Symbol	Disease	Detected method	Sample	Expression	Risk type	Result	Mechanism	PMID	Details
RT1-Da	EAE	N/A	CNS tissue	down-regulation	Disease risk	we could observe reduced protein expression of MHC class II and CIITA in the CNS of the congenic rats fed with vitamin D supplemented diet.	N/A	33304315	Details
CIITA	EAE	N/A	CNS tissue	down-regulation	Disease risk	we could observe reduced protein expression of MHC class II and CIITA in the CNS of the congenic rats fed with vitamin D supplemented diet.	CIITA (Mhc2ta) gene encodes class II transactivator, shown to be essential for MHC class II transcription and expression	33304315	Details
STAT1	MS	Western blot	cerebral tissue	up-regulation	Disease risk	Western blot analysis for total Stat1 and Stat2 proteins was performed at 8 and 24 h poststimulation and show that both IFN-b and IFN-c increase the amounts of total Stat protein expression.	N/A	12437583	Details
STAT2	MS	Western blot	cerebral tissue	up-regulation	Disease risk	Western blot analysis for total Stat1 and Stat2 proteins was performed at 8 and 24 h poststimulation and show that both IFN-b and IFN-c increase the amounts of total Stat protein expression.	N/A	12437583	Details
Elavl4	EAE	Western blot	N/A	up-regulation	Disease risk	Anti-HuR ASO increased the expression of HuD in GAP43-expressing cells and promoted a HuD-mediated neuroprotective activity in MOG–EAE mice.	HuR silencing restored basal levels of HuD protein as well as neuroflament H and GAP43.	36696009	Details
Elavl4	EAE	Western blot	spinal cord	down-regulation	Disease risk	Conversely, HuD was largely downregulated in the MOG–EAE spinal cord.	neuron-specifc proteins involved in neuronal diferentiation	36696009	Details
Elavl1	EAE	Western blot	spinal cord	up-regulation	Disease risk	HuR resulted overexpressed in the spinal cord of MOG35-55–EAE and PLP139-151–EAE mice and was detected in CD11b+cells.	HuR is an ubiquitous protein that, besides neurons, is expressed in activated microglia	36696009	Details
Pomc	EAE	Western blot	blood	up-regulation	Disease risk	Our results reveal an upregulation of Pomc gene expression, followed by POMC and ACTH protein increase at the peak of the EAE in the pituitary.	The increased gene and protein levels of POMC and ACTH in the pituitary lead to increased corticosterone levels.	34220419	Details
Pomc	EAE	Western blot	blood	up-regulation	Disease risk	Our results reveal an upregulation of Pomc gene expression, followed by POMC and ACTH protein increase at the peak of the EAE in the pituitary.	The increased gene and protein levels of POMC and ACTH in the pituitary lead to increased corticosterone levels.	34220419	Details
CCL1	MS	ELISA	blood	up-regulation	Disease risk	Plasma levels of CCL1 were significantly higher in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) than in HTLV-1-seronegative patients with multiple sclerosis (MS) and asymptomatic HTLV-1 healthy carriers (HC).	minocycline inhibited the production of CCL1 in a dose dependent manner in HTLV-1- infected T-cell lines.	29202792	Details
IL25	MS	ELISA	blood	down-regulation	Disease risk	These results demonstrate that serum levels of IL-25 are reduced in MS patients compared to controls.	Considering the role of IL-25 in suppression of the effects of IL-17A and active phase of Experimental Autoimmune Encephalomyelitis (EAE) in vivo	25143869	Details
Ifng	EAE	flow cytometry	brain	up-regulated	Disease risk	Keratinocytes of EAE-susceptible Lewis rats are induced to higher levels of Ia expression compared to relatively resistant Brown-Norway (BN) rats, independent of the dose of IFN-γ applied.	It is now known that the product of Ir genes is the Ia molecule which functions by complexing with antigen in a manner that is recognized by T-cells.	2456308	Details
Ifng	EAE	ELISA	N/A	down-regulated	Disease risk	Collectively, there was a shift in the TH1-TH17 balance in the CNS of Tbx21/ mice during EAE characterized by a tendency toward the recruitment of TH17 cells and a significantly lower frequency and absolute number of IFN-γproducing CD4+ T cells.	TH17 cells produce IL-17A, IL-17F, IL-21 and IL-22	21151104	Details
Il17a	EAE	ELISA	N/A	up-regulated	Disease risk	Moreover, CD4+ T cells isolated from the CNS of Tbx21/ mice secreted significantly more IL-17A than did wild-type CD4+ T cells at day 17 after immunization.	TH17 cells produce IL-17A, IL-17F, IL-21 and IL-22	21151104	Details
Tbx21	EAE	ELISA	N/A	down-regulated	Disease risk	high zinc aspartate concentrations was signifcantly impaired indicated by reduced expression of the T1 transcription factor Tbet and the T1 signature cytokine IFN-γ as well as of the cytokines IL-2 and TNF-αT1 cells and transferring them into C57BL/6 recipient mice.	transcription factor	35121767	Details
Ifng	EAE	ELISA	N/A	down-regulated	Disease risk	high zinc aspartate concentrations was signifcantly impaired indicated by reduced expression of the T1 transcription factor Tbet and the T1 signature cytokine IFN-γ as well as of the cytokines IL-2 and TNF-αT1 cells and transferring them into C57BL/6 recipient mice.	inflammatory cytokines	35121767	Details
Il2	EAE	ELISA	N/A	down-regulated	Disease risk	high zinc aspartate concentrations was signifcantly impaired indicated by reduced expression of the T1 transcription factor Tbet and the T1 signature cytokine IFN-γ as well as of the cytokines IL-2 and TNF-αT1 cells and transferring them into C57BL/6 recipient mice.	inflammatory cytokines	35121767	Details
Tnf	EAE	ELISA	N/A	down-regulated	Disease risk	high zinc aspartate concentrations was signifcantly impaired indicated by reduced expression of the T1 transcription factor Tbet and the T1 signature cytokine IFN-γ as well as of the cytokines IL-2 and TNF-αT1 cells and transferring them into C57BL/6 recipient mice.	pro-inflammatory cytokines	35121767	Details
IL10	MS	ELISA	blood	down-regulated	Disease risk	The plasma levels of IL-10, IL-27 and TGF-β in MS patients were significantly lower than healthy controls (p<0.001, p<0.001, and p=0.013).	inhibitory cytokines	25780887	Details
IL27	MS	ELISA	blood	down-regulated	Disease risk	The plasma levels of IL-10, IL-27 and TGF-β in MS patients were significantly lower than healthy controls (p<0.001, p<0.001, and p=0.013).	inhibitory cytokines	25780887	Details
TGFB1	MS	ELISA	blood	down-regulated	Disease risk	The plasma levels of IL-10, IL-27 and TGF-β in MS patients were significantly lower than healthy controls (p<0.001, p<0.001, and p=0.013).	inhibitory cytokines	25780887	Details
IL10	MS	ELISA	blood	down-regulated	Disease risk	Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p = 0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR.	Th2 cytokines	25173940	Details
IL4	MS	ELISA	blood	down-regulated	Disease risk	Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p = 0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR.	Th2 cytokines	25173940	Details
IL17A	MS	ELISA	blood	up-regulated	Disease risk	Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p = 0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR.	Th17 cytokine	25173940	Details
IFNG	MS	ELISA	blood	up-regulated	Disease risk	Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p = 0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR.	Th1 cytokine	25173940	Details
TNF	MS	ELISA	blood	up-regulated	Disease risk	Males carrying the TNFB2/B2 genotype exhibited increased levels of TNF-α, IFN-γ, and IL-17 (p = 0.0326) and decreased levels of IL-4, IL-10, insulin, and HOMA-IR.	pro-inflammatory cytokines	25173940	Details
Ifng	EAE	N/A	brain	down-regulated	Disease risk	we analyzed cytokine expression in the lesions and also determined whether B10.M mice can respond to peptides derived from the DR3 molecule. Intense staining for IFN-g and IL-4, T helper (TH) 1 and TH2 cytokines, respectively, was found in the lesions of TMEV-infected DR32 mice but not in the DR31 transgenic mice at day 21 after infection.	N/A	9541508	Details
Il4	EAE	N/A	brain	down-regulated	Disease risk	we analyzed cytokine expression in the lesions and also determined whether B10.M mice can respond to peptides derived from the DR3 molecule. Intense staining for IFN-g and IL-4, T helper (TH) 1 and TH2 cytokines, respectively, was found in the lesions of TMEV-infected DR32 mice but not in the DR31 transgenic mice at day 21 after infection.	N/A	9541508	Details
IL4	MS	N/A	blood	up-regulated	Disease risk	Interestingly, six out of 12 T-cell lines from the three anti-MOGIgd antibody-seropositive donors (HK, CL, ASt) produced significant amounts of IL-4 after stimulation (Th-0 or Th-2subset responses).	N/A	10545394	Details
HPSE	EAE	Western blot	spleen	up-regulated	disease risk	Regulation of heparanase expression in T cells and EAE	The expression of Hpse in endothelial cells suggests that the enzyme may also contribute to the progression of disease in a non-T lymphocyte manner.	17656651	Details
Ifng	EAE	ELISA	spleen	up-regulated	disease risk	In contrast, splenic T cells from CD11d/ mice produced two-fold greater levels of IFN-γ, but lower levels of TNF-α compared to control mice.	N/A	17254640	Details
Tnf	EAE	ELISA	spleen	down-regulated	disease risk	In contrast, splenic T cells from CD11d/ mice produced two-fold greater levels of IFN-γ, but lower levels of TNF-α compared to control mice.	N/A	17254640	Details
IFNB1	MS	ELISA	N/A	up-regulated	treatment risk	IFN-b is increased in ELISA of serum samples of MS patients during relapse.	N/A	25261476	Details
Il17a	EAE	ELISA	N/A	down-regulated	disease risk	miR-155 Is Required for Inflammatory T Cell Development during the Induction Phase of EAE	N/A	20888269	Details
Ifng	EAE	ELISA	N/A	down-regulated	disease risk	miR-155 Is Required for Inflammatory T Cell Development during the Induction Phase of EAE	N/A	20888269	Details
Il6	EAE	ELISA	N/A	down-regulated	disease risk	miR-155 Is Required for Inflammatory T Cell Development during the Induction Phase of EAE	N/A	20888269	Details
Csf2	EAE	ELISA	N/A	down-regulated	disease risk	miR-155 Is Required for Inflammatory T Cell Development during the Induction Phase of EAE	N/A	20888269	Details
Il17a	EAE	ELISA	peripheral lymphoid organs	down-regulated	disease risk	DRG2 overexpression decreases the TH17 population and expression levels of proinflammatory cytokines in peripheral blood cells.	Autoantigen-specific TH1 and TH17 lineages have been shown to mediate EAE.	24463315	Details
Il6	EAE	ELISA	peripheral lymphoid organs	down-regulated	disease risk	DRG2 overexpression decreases the TH17 population and expression levels of proinflammatory cytokines in peripheral blood cells.	Autoantigen-specific TH1 and TH17 lineages have been shown to mediate EAE.	24463315	Details
Ifng	EAE	ELISA	peripheral lymphoid organs	down-regulated	disease risk	DRG2 overexpression decreases the TH17 population and expression levels of proinflammatory cytokines in peripheral blood cells.	Autoantigen-specific TH1 and TH17 lineages have been shown to mediate EAE.	24463315	Details
Tnf	EAE	ELISA	peripheral lymphoid organs	down-regulated	disease risk	DRG2 overexpression decreases the TH17 population and expression levels of proinflammatory cytokines in peripheral blood cells.	Autoantigen-specific TH1 and TH17 lineages have been shown to mediate EAE.	24463315	Details
Ccl2	EAE	ELISA	peripheral lymphoid organs	down-regulated	disease risk	DRG2 overexpression decreases the TH17 population and expression levels of proinflammatory cytokines in peripheral blood cells.	Autoantigen-specific TH1 and TH17 lineages have been shown to mediate EAE.	24463315	Details
EAAT-2	EAE	Western blot	spinal cord	down-regulated	disease risk	There is a significant decrease in the levels of spinal EAAT-2 mice with EAE when compared to CFA. All samples are taken at disease onset.	Interestingly, IL-6 is also known to be a major factor triggering the downregulation of EAAT-2.	23291347	Details
Ifng	EAE	flow cytometry	Serum	up-regulated	Disease risk	C57BL/6 mice that developed EAE after immunization with MOG3555 experienced a significant increase in the percentage of CD4+ T cells producing IFN-gamma.	Upregulation of B and, to a lesser extent, of Treg, is closely associated with MHCindependent resistance to MOG-induced EAE in CD1 mice and with the abrogation of both Th1 and Th17 responses.	24868560	Details
Il17a	EAE	flow cytometry	Serum	up-regulated	Disease risk	Only C57BL/6 mice that developed EAE after immunization with MOG3555 displayed a significant increase in the percentage of CD4+ T cells producing IL-17.	Upregulation of B and, to a lesser extent, of Treg, is closely associated with MHCindependent resistance to MOG-induced EAE in CD1 mice and with the abrogation of both Th1 and Th17 responses.	24868560	Details
Stat1	EAE	Western blot	brain	up-regulated	Disease risk	In contrast with the GF-IL12 mice, infiltrating mononuclear cells in EAE displayed high levels of STAT1 protein.	N/A	11786421	Details
Ifng	EAE	ELISA	Serum	up-regulated	Disease risk	Cytokine analysis revealed an increase in pro-inˉammatory (IFN g, IL-12 and IL-6) and antiinˉammatory (IL-10) cytokines.	In most forms of EAE, the Th1 cells or Th1 cytokines promote disease, while Th2 cells or cytokines down-regulate disease.	12663683	Details
Il12a	EAE	ELISA	Serum	up-regulated	Disease risk	Cytokine analysis revealed an increase in pro-inˉammatory (IFN g, IL-12 and IL-6) and antiinˉammatory (IL-10) cytokines.	In most forms of EAE, the Th1 cells or Th1 cytokines promote disease, while Th2 cells or cytokines down-regulate disease.	12663683	Details
Il6	EAE	ELISA	Serum	up-regulated	Disease risk	Cytokine analysis revealed an increase in pro-inˉammatory (IFN g, IL-12 and IL-6) and antiinˉammatory (IL-10) cytokines.	In most forms of EAE, the Th1 cells or Th1 cytokines promote disease, while Th2 cells or cytokines down-regulate disease.	12663683	Details
Il10	EAE	ELISA	Serum	up-regulated	Disease risk	Cytokine analysis revealed an increase in pro-inˉammatory (IFN g, IL-12 and IL-6) and antiinˉammatory (IL-10) cytokines.	In MOG-induced EAE, it is speculated that Th2 cytokines play a role in disease severity, recovery and remission.	12663683	Details
Tnf	EAE	ELISA	blood vessels	down-regulated	Disease risk	SA13353 attenuated cytokine levels, including TNF-α, IL-1β, IL-12p40,IL-17, and IFN-γ	These results suggest that TRPV1 agonists may act as anti-inflammatory and immunomodulatory agents in vivo in certain inflammatory diseases.	19878665	Details
Il1b	EAE	ELISA	blood vessels	down-regulated	Disease risk	SA13353 attenuated cytokine levels, including TNF-α, IL-1β, IL-12p40,IL-17, and IFN-γ	These results suggest that TRPV1 agonists may act as anti-inflammatory and immunomodulatory agents in vivo in certain inflammatory diseases.	19878665	Details
Il12b	EAE	ELISA	blood vessels	down-regulated	Disease risk	SA13353 attenuated cytokine levels, including TNF-α, IL-1β, IL-12p40,IL-17, and IFN-γ	These results suggest that TRPV1 agonists may act as anti-inflammatory and immunomodulatory agents in vivo in certain inflammatory diseases.	19878665	Details
Il17a	EAE	ELISA	blood vessels	down-regulated	Disease risk	SA13353 attenuated cytokine levels, including TNF-α, IL-1β, IL-12p40,IL-17, and IFN-γ	These results suggest that TRPV1 agonists may act as anti-inflammatory and immunomodulatory agents in vivo in certain inflammatory diseases.	19878665	Details
Ifng	EAE	ELISA	blood vessels	down-regulated	Disease risk	SA13353 attenuated cytokine levels, including TNF-α, IL-1β, IL-12p40,IL-17, and IFN-γ	These results suggest that TRPV1 agonists may act as anti-inflammatory and immunomodulatory agents in vivo in certain inflammatory diseases.	19878665	Details
Il17a	EAE	ELISA	N/A	up-regulated	Disease risk	In addition, SA13353 attenuated the increase of IL-17 production in splenocytes.	These results suggest that TRPV1 agonists may act as anti-inflammatory and immunomodulatory agents in vivo in certain inflammatory diseases.	19878665	Details
Lta	EAE	N/A	spleen	up-regulated	Disease risk	Expression of cytokines TNF-b and LT-b preceded, and the expression of TGF-b1 followed chemokine upregulation.	N/A	12828562	Details
Ltb	EAE	N/A	spleen	up-regulated	Disease risk	Expression of cytokines TNF-b and LT-b preceded, and the expression of TGF-b1 followed chemokine upregulation.	N/A	12828562	Details
Tgfb1	EAE	N/A	spleen	up-regulated	Disease risk	Expression of cytokines TNF-b and LT-b preceded, and the expression of TGF-b1 followed chemokine upregulation.	It was demonstrated in EAE that systemic administration of TGF-b ameliorated the symptoms of the disease.	12828562	Details
Tgfb1	EAE	ELISA	lymph node	down-regulated	Disease risk	Notably, the production of the immunosuppressive cytokine TGF-1b was significantly diminished in culture supernatants of both unstimulated and MOG p35–55-stimulated lymph node cells obtained from MOG-primed CD26-/- animals in comparison with cells from CD26-/-wild-type mice.	this lack of intrinsic TGF-β1 release may cause exacerbation of EAE.	17372022	Details
Ifng	EAE	ELISA	lymph node	up-regulated	Disease risk	Levels of IFN-g, IL-2, and TNF-a in these cultures were measured by specific ELISA.	As these cytokines are associated with the encephalitogenic potency of myelin Ag-specific T cells, we conclude that enhanced Th1 cell reactivity in response to MOG is part of the underlying mechanism causing enhanced disease scores in CD26-/- mice.	17372022	Details
Il2	EAE	ELISA	lymph node	up-regulated	Disease risk	Levels of IFN-g, IL-2, and TNF-a in these cultures were measured by specific ELISA.	As these cytokines are associated with the encephalitogenic potency of myelin Ag-specific T cells, we conclude that enhanced Th1 cell reactivity in response to MOG is part of the underlying mechanism causing enhanced disease scores in CD26-/- mice.	17372022	Details
Tnf	EAE	ELISA	lymph node	up-regulated	Disease risk	Levels of IFN-g, IL-2, and TNF-a in these cultures were measured by specific ELISA.	As these cytokines are associated with the encephalitogenic potency of myelin Ag-specific T cells, we conclude that enhanced Th1 cell reactivity in response to MOG is part of the underlying mechanism causing enhanced disease scores in CD26-/- mice.	17372022	Details
IL33	MS	ELISA	blood	up-regulated	Disease risk	the level of IL33 was significantly higher in patients with asthma (3767.5±1139.8 pg/ml) and MS.	Thus, increased expression of IL-33 in MS might have an important role in the activation of mast cells that could secrete neurotoxin molecules, increase the permeability of the blood-brain barrier and activate immune cells.	30950351	Details
DNMT1	MS	Western blot	peripheral blood	down-regulated	Disease risk	We show that TET2 and DNMT1 expression is significantly down-regulated in MS PBMCs and it is associated with aberrant methylation of their promoters.	Furthermore, 5hmC is decreased in MS PBMCs, probably as a result of the diminished TET2 level.	24735979	Details
TET2	MS	Western blot	peripheral blood	down-regulated	Disease risk	We show that TET2 and DNMT1 expression is significantly down-regulated in MS PBMCs and it is associated with aberrant methylation of their promoters.	Furthermore, 5hmC is decreased in MS PBMCs, probably as a result of the diminished TET2 level.	24735979	Details
LILRA3	MS	ELISA	blood	up-regulated	Disease risk	LILRA3 protein level was significantly increased in sera of patients with MS when compared with control subjects, particularly in more severe type primary progressive MS.	Taken together our results indicate that LILRA3 is not a risk variant in MS susceptibility but is involved in modulating inflammation thereby contributing to the variability in disease severity and/or clinical outcomes.	26871720	Details
Aif1	EAE	ELISA	N/A	up-regulated	Disease risk	Immunolocalization of AIF-1 in EAU, EAN, and EAE. In autoimmune lesions AIF-1 expression is strikingly enhanced.	N/A	9728770	Details
Ccl6	EAE	immunohistochemistry	brain	up-regulated	Disease risk	Notably, high expression of C10 and C10-related genes was found in the cerebellum and spinal cord of GFAP-IL3 mice with inflammatory demyelinating disease and in mice with experimental autoimmune encephalomyelitis.	C10 is a prominent chemokine expressed in the central nervous system in experimental inflammatory demyelinating disease that, we show, also acts as a potent chemotactic factor for the migration of these leukocytes to the brain.	10233856	Details
KIF5A	MS	immuno-dot blot	grey matter tissue	down-regulated	Disease risk	We found a significant reduction in KIF5A and associated cargoes in MS white matter.	N/A	26785938	Details
Ifng	EAE	ELISA	N/A	up-regulated	Disease risk	T cells from PLP91–110 peptide-immunized DR3.DQ6.Aβ° and DQ6.Aβ° mice produced high levels of IFN-g compared with DR3.Aβ° mice, while T cells from DR3.Aβ° produced increased levels of IL-6, IL-12, and TNF-γ.	N/A	18490779	Details
Il6	EAE	ELISA	N/A	up-regulated	Disease risk	T cells from PLP91–110 peptide-immunized DR3.DQ6.Aβ° and DQ6.Aβ° mice produced high levels of IFN-g compared with DR3.Aβ° mice, while T cells from DR3.Aβ° produced increased levels of IL-6, IL-12, and TNF-γ.	N/A	18490779	Details
Il12a	EAE	ELISA	N/A	up-regulated	Disease risk	T cells from PLP91–110 peptide-immunized DR3.DQ6.Aβ° and DQ6.Aβ° mice produced high levels of IFN-g compared with DR3.Aβ° mice, while T cells from DR3.Aβ° produced increased levels of IL-6, IL-12, and TNF-γ.	N/A	18490779	Details
Tnf	EAE	ELISA	N/A	up-regulated	Disease risk	T cells from PLP91–110 peptide-immunized DR3.DQ6.Aβ° and DQ6.Aβ° mice produced high levels of IFN-g compared with DR3.Aβ° mice, while T cells from DR3.Aβ° produced increased levels of IL-6, IL-12, and TNF-γ.	N/A	18490779	Details
Tet1	EAE	Western Blot	SC tissue	down-regulation	Disease risk	We found that Tet1 and Tet2 protein significantly decreased at day 28 after EAE induction.	Therefore, the reduced expression of Tet1 and Tet2 protein represents an important cause of MS-induced myelin damage that leads to the decrease of DNA 5hmC in EAE-induced nontraumatic SC damage.	30426768	Details
Tet2	EAE	Western Blot	SC tissue	down-regulation	Disease risk	We found that Tet1 and Tet2 protein significantly decreased at day 28 after EAE induction.	Therefore, the reduced expression of Tet1 and Tet2 protein represents an important cause of MS-induced myelin damage that leads to the decrease of DNA 5hmC in EAE-induced nontraumatic SC damage.	30426768	Details
Il2	EAE	ELISA	the hind footpad and base of tail	down-regulation	Disease risk	Thus, PLP139 –151-specific T cells have a dra matically reduced capacity to proliferate or secrete IL-2 following treatment with 145D, and there is an absence of deviation in cy tokine production.	These data suggest that autoreactive T cells may be rendered anergic in vivo upon encountering less stable MHC variant peptides and thereby be less capable of mediating EAE.	15749867	Details
Il17a	EAE	ELISA	CNS tissue	down-regulation	Disease risk	CNS inflammatory cells from P. histicola treated group had reduced levels of inflammatory cytokines IFN-γ and IL-17 as measured by ELISA (F) and flow cytometry (G and H) compared with the medium treated group.	P. histicola challenge led to a decrease in pro inflammatory Th1 and Th17 cells, and increase in the frequencies of CD4+FoxP3+ regulatory T cells, tolerogenic dendritic cells, and suppressive macrophage.	28793252	Details
Ifng	EAE	ELISA	CNS tissue	down-regulation	Disease risk	CNS inflammatory cells from P. histicola treated group had reduced levels of inflammatory cytokines IFN-γ and IL-17 as measured by ELISA (F) and flow cytometry (G and H) compared with the medium treated group.	P. histicola challenge led to a decrease in pro inflammatory Th1 and Th17 cells, and increase in the frequencies of CD4+FoxP3+ regulatory T cells, tolerogenic dendritic cells, and suppressive macrophage.	28793252	Details
Gata3	EAE	ELISA	brain	up-regulation	Disease risk	Noticeably,treatment with combination of L. plantarum and B. animalis strains showed the highest expression level of GATA3and Foxp3mRNA level along with the lowest level of inflammatory tran scription factors, T-bet and ROR-γt, along the all treatment groups and PBS-treated mice.	N/A	28946394	Details
Foxp3	EAE	ELISA	brain	up-regulation	Disease risk	Noticeably,treatment with combination of L. plantarum and B. animalis strains showed the highest expression level of GATA3and Foxp3mRNA level along with the lowest level of inflammatory tran scription factors, T-bet and ROR-γt, along the all treatment groups and PBS-treated mice.	N/A	28946394	Details
Tbx21	EAE	ELISA	brain	down-regulation	Disease risk	Noticeably,treatment with combination of L. plantarum and B. animalis strains showed the highest expression level of GATA3and Foxp3mRNA level along with the lowest level of inflammatory tran scription factors, T-bet and ROR-γt, along the all treatment groups and PBS-treated mice.	N/A	28946394	Details
Rorc	EAE	ELISA	brain	down-regulation	Disease risk	Noticeably,treatment with combination of L. plantarum and B. animalis strains showed the highest expression level of GATA3and Foxp3mRNA level along with the lowest level of inflammatory tran scription factors, T-bet and ROR-γt, along the all treatment groups and PBS-treated mice.	N/A	28946394	Details
Lcn2	EAE	Western blot	brain	up-regulation	Disease risk	We show that Lcn2 is significantly upregulated in the spinal cord throughout EAE and is expressed predominantly by monocytes and reactive astrocytes.	Lcn2 is a multi-functional protein that plays a role in glial activation, matrix metalloproteinase(MMP) stabilization, and cellular iron flux.	22499213	Details
Il6	EAE	ELISA	spinal cords	down-regulation	Disease risk	ELISA data confirmed the reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point.	we showed previously that depletion of γδT cells using the mAb GL3 immediately before disease onset, or during the chronic phase, significantly ameliorated clinical severity.	9637509	Details
Il1	EAE	ELISA	spinal cords	down-regulation	Disease risk	ELISA data confirmed the reduced levels of IL-1 and IL-6 at disease onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point.	we showed previously that depletion of γδT cells using the mAb GL3 immediately before disease onset, or during the chronic phase, significantly ameliorated clinical severity.	9637509	Details
Tsc22d3	EAE	ELISA	N/A	up-regulation	Disease risk	Endogenous regulator (GILZ) expression by splenic DCs isolated from EAE mice treated with HGF.	In this study,we demonstrate that systemic HGF treatment ameliorates EAE through the development of tolerogenic dendritic cells (DCs) with high expression levels of glucocorticoid-induced leucine zipper (GILZ), a transcriptional repressor of gene expression and a key endogenous regulator of the inflammatory response.	25114100	Details
Il17a	EAE	ELISA	brain	up-regulation	Disease risk	Astrocytes up-regulated IL-17 and IFN-γ gene expression and protein synthesis in T cells.	N/A	17969033	Details
Ifng	EAE	ELISA	brain	up-regulation	Disease risk	Astrocytes up-regulated IL-17 and IFN-g gene expression and protein synthesis in T cells.	N/A	17969033	Details
PLTP	MS	Western Blot Analysis	whole blood	up-regulation	Disease risk	We have identified the anomaly as the phospholipid transfer protein by western blot using antiphospholipid transfer antibodies. Activity assays showed that the phospholipid transfer activity was elevated in fasted plasma samples from subjects with MS compared to controls.	Alterations in metabolic pathways in subjects with MS have been suggested before .These include abnormalities in the plasma proteins, reduced levels of lecithin cholesterol acyltransferase in the brain, alterations in plasma and cellular lipid profiles, and differences in the phospholipid content of normal myelin compared with myelin from subjects with MS.PLTP transfers phospholipids but lacks the ability to transfer either CE or TG.Both CETP and PLTP have been detected in plasma and cerebrospinal fluid (CSF) where they play important roles in maintaining lipid homeostasis.	26347820	Details
CCR7	EAE	flow cytometry	T cells	down-regulation	Disease risk	Indeed, co-culture with B-LCLs induced significant reduction of CCR7+ T cells in MNC isolated from animals that had developed clinically evident EAE, whereas no effect was observed on the percentage of CCR7+ T cells in MNC isolated from marmosets that failed to develop clinically evident EAE.	N/A	28243437	Details
IL10	MS	ELISA	peripheral blood leukocytes	No significance	Disease risk	No statistically significant differences were observed between two groups.	IL-10 is an important cytokine regulator of the immune system, secreted mainly by macrophages and T lymphocytes.It is involved in the immune response to infectious and autoimmune diseases.IL-10 has an anti-inflammatory effect by reducing the production of immunoactive molecules (TNF-α, IFNγ, and IL-12) and inhibiting antigen-specific cytotoxic T cells.Since IL-10 may have an inflammatory function, it activates B cells and promotes autoantibody production.In the absence of IL-2, it inhibits T-cell apoptosis and promotes T-cell growth . It has been shown to increase the productivity of IL-10-producing cells.	35741685	Details
OPA1	MS	Western Blotting	PBMC	No significance	Disease risk	Densitometric analysis of immuno-revealed bands of OPA1 (L+S) showed the same level of total OPA1protein in MS group with respect to HC.No difference was observed in percentage of L and S form of OPA1 between HC and SM samples.No differences were observed in Rf of L-OPA1 between HC and MS samples .	Increase of reactive oxygen species (ROS), impairment of mitochondria-mediated apoptosis and mitochondrial alterations have been reported in peripheral lymphocytes of MS patients.Mitochondria-mediated apoptosis is regulated by several mechanisms and proteins.Among others, optic atrophy 1 (OPA1) protein plays a key role in the regulating mitochondrial dynamics, cristae architecture and release of pro-apoptotic factors.	32290388	Details
PHB2	MS	Western Blotting	PBMC	up-regulation	Disease risk	An increased PHB2 protein level was observed in MS patients.	OPA1 stability is controlled by prohibitin 2 (PHB2) a chaperon like protein, localizes in nucleus, plasma membrane, and mitochondria.Evidences indicate that mitochondrial PHB2 is over expressed under conditions of oxidative stress.	32290388	Details
SIRT3	MS	Western Blotting	PBMC	No significance	Disease risk	No difference was observed for SIRT3 protein level.	OPA1 processing is also modulated by its acetylation status mediated by SIRT3 enzyme, a mitochondrial deacetylase that also plays an important role in apoptosis .	32290388	Details
Entpd2	EAE	Immunofluorescence	spinal cord	down-regulation	Disease risk	During the course of EAE, the intensity of NTPDase2-ir visibly decreased in the white matter .	For MS/EAE to develop, the coordinated action of several immune and neural cell types is required.ATP initiates and coordinates a cross-talk between infiltrated T-cells and resident microglia and astrocytes, by recruiting T cells and facilitating their extravasation into the CNS, potentiating the release of cytokines and chemokines and activating and attracting microglia and astrocytes, which govern further pathology in MS.Moreover, ATP activates low-affinity P2X7 receptors and potentiates the release of interleukin-1β and cyclooxygenase induction, causing demyelination,oligodendrocyte death and axonal damage.Extracellular ATP is eliminated by the coordinated action of ectonucleotidase enzyme cascade.An ectonucleotidase, with specific substrate affinity and restricted expression in the brain is ectonucleoside triphosphate diphosphohydrolase-2 (NTPDase2;previously known as Ecto-ATPase, or CD39L1).The enzyme preferentially catalyzes the dephosphorylation of ATP to ADP, generating a ligand for P2Y1, P2Y12 and P2Y13 receptors.There is compelling evidence for the critical involvement of purinergic signaling in the control of different aspects of MS/EAE pathophysiology.	29163045	Details
MMP9	MS	ELISA	serum	up-regulation	Disease risk	A significant elevation in MMP-9 serum levels was found in the whole MS group, in the RRMS, and SPMS groups when compared with the controls.	Matrix metalloproteinases (MMPs) play an important role in the immunopathogenesis and progression of disease. It has been suggested that an imbalance between MMP and TIMP expression may lead to persistent proteolytic activity with subsequent continuous tissue destruction in various diseases, including MS. In the immunopathogenesis of MS, metalloproteinases are involved in the disruption of the blood-brain barrier (BBB), invasion of immune cells into the CNS parenchyma, degradation of the basic myelin protein, and direct neurotoxicity.	19153173	Details
MMP2	MS	ELISA	serum	up-regulation	Phenotypic risk	A significant elevation in MMP-2 serum levels was observed in the primary progressive and the SPMS groups when compared with the RRMS group, and this increase was also associated with the disability and severity of the disease.	Matrix metalloproteinases (MMPs) play an important role in the immunopathogenesis and progression of disease. It has been suggested that an imbalance between MMP and TIMP expression may lead to persistent proteolytic activity with subsequent continuous tissue destruction in various diseases, including MS. In the immunopathogenesis of MS, metalloproteinases are involved in the disruption of the blood-brain barrier (BBB), invasion of immune cells into the CNS parenchyma, degradation of the basic myelin protein, and direct neurotoxicity.	19153173	Details
IL32	MS	quantitative sandwich enzyme immunoassay	antecubital vein	up-regulation	Disease risk	Serum levels of IL-32 were significantly different between MS patients and controls. IL-32 was dramatically higher in the patients than that healthy controls.	IL-32, a pluripotent proinflammatory cytokine, may have a role in intensifying the inflammation. It has the double effects on inflammation through augmentation of secretion various inflammatory cytokines as well as enhancing cells migration to the site of inflammation.	28716229	Details
Ndrg2	EAE	western blotting,immunohistochemistry	lumbar spinal cords	up-regulation	Disease risk	The NDRG2 expression levels were significantly increased in both the acute and chronic periods after EAE induction (Fig. 1a), when the levels of GFAP, which is the most commonly used marker of activated astrocytes, were also increased	N/A	29315585	Details
IL27	MS	ELISA	serum	down-regulation	Disease risk	IL27 levels were significantly lower in patients compared to controls.	IL27 is a novel member of the IL12 family, known for both its pro- and anti-inflammatory functions, with distinct roles in shaping the activity of T-cells. IL27 regulates the immune response through its heterodimeric IL27Ra/GP130 receptor, activating multiple signaling cascades.In the brain, IL27 produced by astrocytes and microglial cells is recognized for its neuroprotective effects, enhancing the production of nerve growth factor and neurotrophic factor, promoting remyelination.	34410977	Details
C3	MS	single radial immunodiffusion with monospecific sera	serum	down-regulation	Disease risk	The frequency of low C3 is significantly higher in MS than that found in the normal group.	We recently suggested that hypocomplementaemic MS is a specific form of the disease.The hypocomplementaemic population is statistically associated with low factor B and IgG levels, a low cerebrospinal fluid (CSF) IgG ratio, a pure remittent form of evolution, early age of onset, increased frequency of infectious events prior to MS and a fairly benign prognosis.	886365	Details
CFB	MS	single radial immunodiffusion with monospecific sera	serum	down-regulation	Disease risk	Factor B is low in 63.3 % of the cases.	We recently suggested that hypocomplementaemic MS is a specific form of the disease.The hypocomplementaemic population is statistically associated with low factor B and IgG levels, a low cerebrospinal fluid (CSF) IgG ratio, a pure remittent form of evolution, early age of onset, increased frequency of infectious events prior to MS and a fairly benign prognosis.	886365	Details
ELAVL1	MS	immunohistochemistry	occipital lobe and medulla oblongata	up-regulation	Disease risk	It was highly expressed in the border zone of MS plaques, but weakly expressed in the center of demyelinating plaques.In addition, HuR expression in microglia was significantly greater in the border area of MS plaques compared to that in the center area or normal myelin area.	HuR stabilizes cystatin F expression in the border zone of MS plaques in demyelinating disorders.	32947653	Details
NECTIN2	MS	flow cytometry	PBMCs	No significance	Disease risk	The studies did not disclose any expression difference between MS patients and controls for the protein on peripheral blood monocytes.	HVEB mediates entry of neurotropic viruses to the brain.In the CNS, both receptors are structural CNS proteins and important for cellular interactions.	15465608	Details
PVR	MS	flow cytometry	PBMCs	No significance	Disease risk	The studies did not disclose any expression difference between MS patients and controls for the protein on peripheral blood monocytes.	PVR mediates entry of neurotropic viruses to the brain.Functional PVR, called the bona fide receptor, is essential for entry of the polio virus in neurons. In the CNS, both receptors are structural CNS proteins and important for cellular interactions.	15465608	Details
CX3CR1	MS	flow cytometric analyses	PBMCs	down-regulation	Disease risk	The data confirm that MS patients showed a reduced CX3CR1 protein expression compared with control individuals.	The reduced frequency of CX3CR1 NK cells demonstrated in our study might imply the presence of a defective cytotoxic effector NK cell population in MS patients. NK cells appear to be essential in regulating the immune response and in the development of autoimmune processes.	16144955	Details
PTGDS	MS	sandwich ELISA	CSF	No significance	Disease risk	The L-PGDS level in the CSF of MS patients was not considered to be significantly increased from normal level.	Prostaglandin (PG) D2 is a major PG in the central nervous system (CNS) and functions as a neuromodulator mediating the regulation of the sleep–wake cycle, body temperature, hormone release and pain responses. In the CNS, PGD2 is constitutively synthesized by lipocalin-type PGD synthase (L-PGDS), which is dominantly localized in leptomeningeal cells, and is secreted into the cerebrospinal fluid (CSF) as b-trace, a major protein in the human CSF.	16409554	Details
CD40	MS	flow cytometry	PBMCs	down-regulation	Disease risk	Comparison of B lymphocyte expression of CD40 in MS patients failed to show a significant effect of genotype on surface CD40 expression levels in total B lymphocytes, nave B lymphocytes or classical memory B lymphocytes.However, comparison of cell surface CD40 expression on B-lymphocytes between healthy controls and MS patients showed that CD40 expression was significantly lower in MS patients compared to healthy controls in all CD19+ B-lymphocytes, as well as in the nave B lymphocytes, classical memory B-lymphocyte and IgM memory B lymphocyte subsets.A subset comparison of patients and unaffected controls homozygous for the rs1883832 C allele (CC) also demonstrated a significant decrease in CD40 expression on the total B—lymphocytes of MS patients compared to controls.	N/A	26068105	Details
ERVW-1	MS	Flow Cytometry	peripheral blood	up-regulation	Disease risk	pHERV-W ENV/syncytin-1 protein expression levels were significantly higher in MS patients compared to HD.Relating to PP-MS patients, they showed significantly higher protein expression levels in monocytes and NK cells compared to HD.Moreover, these patients showed significantly higher pHERV-W ENV/syncytin-1 protein expression levels in monocytes compared to RR-MS patients.	The HERV-W family, and its two main members (multiple sclerosis-associated retrovirus, MSRV, and ERVWE1), have been the most studied ones concerning MS. ERVWE1 envelope protein (env), called syncytin-1, is a fusogenic protein essential for placental syncytiotrophoblast formation.In relation to MS, proinflammatory and neurotoxic properties of pHERV-W ENV could lead to the development and progression of the disease.	34912348	Details
Slc1a3	cuprizone-induced demyelination	Western blot analysis	corpus callosum	up-regulation	Disease risk	30% higher protein levels of GLAST in the demyelinated CC compared to controls.	Excitotoxicity is associated with a wide range of acute neurological and chronic neurodegenerative disorders .In the adult central nervous system (CNS), glutamate uptake from the extracellular space is predominantly controlled by the astroglialtransporters, excitatory amino acid transporter 1 (EAAT1) and EAAT2, which are known in the rat brain as GLAST and glutamate transporter-I (GLT-I), respectively.Glutamate signaling also seems to be involved in the pathology and repair of demyelinating disorders such as multiple sclerosis (MS).	23711509	Details
IL1B	MS	ELISA	PBMC	No significance	Disease risk	Normalized ILβ1 protein levels did not differ between HC and MS patients.	Pathogenic Th17 cells can be induced by a cytokine cocktail containing IL-1β, which is a potent pro-inflammatory cytokine.	25458313	Details
IL1R1	MS	ELISA	PBMC	up-regulation	Disease risk	Normalized IL-1Ra protein levels were increased in MS patients compared to HC.	Since IL-1β is an extremely potent pro-inflammatory molecule, its secretion and effector functions need to be tightly regulated. However, also outside the cell, IL-1β activity is tightly regulated. Like IL-1β, the IL-1 receptor antagonist (IL-1Ra) binds to the IL-1 receptor (IL-1R) resulting in competition for binding to this receptor.	25458313	Details
GRN	MS	ELISA	CSF	No significance	Disease risk	No statistically significant differences were found in patients compared with either NIND, OIND or CON, even stratifying according to disease subtype or gender.	Multiple sclerosis (MS) is considered predominantly an inflammatory autoimmune disease of the central nervous system (CNS), with myelin proteins supposed to act as autoantigens, starting with aberrant activation of specific populations of autoreactive T lymphocytes in the periphery, followed by T cell recruitment into the brain.In fact, despite the full length protein displays trophic properties, its proteolitically derived peptides (granulins) act as pro-inflammatory mediators.Other evidence can be found about increased levels of GRN mRNA in several inflammatory neurodegenerative disorders associated with microglial activation such as ALS and virally induced CNS inflammation.Neuronal death is the pathological correlate of disease progression in multiple sclerosis.	19963041	Details
IGHV4-34	MS	ELISA	serum	No significance	Disease risk	Diseases such as multiple sclerosis (MS) display no increase in VH4-34 Ig.	The human immunoglobulin heavy chain gene VH4- 34 is known to encode autoantibodies.Mediated principally by autoimmune T cells, these diseases do not stimulate natural immunity and thus may not be associated with activating the first line of defense response.	15598986	Details
RFX5	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	RFX5 was expressed at a moderate level in microglial cells and astrocytes of normal control brain tissue.The phagocytic macrophages in the lesions were strongly positive for RFX5 expression.	RFX is specific for and directly involved in the expression of MHC genes.	11571785	Details
CIITA	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	CIITA was also moderately expressed in microglial cells, but weakly in astrocytes, and not in endothelial cells of the blood vessel walls in brain tissue of normal control cases. The phagocytic macrophages in the lesions were moderately positive for CIITA expression .	The coactivator CIITA is specific for and directly involved in the expression of MHC genes.	11571785	Details
NFKB1	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	In microglial cells localized in normal control white matter, the NF-kB p50 and p65 subunits were expressed at weak to moderate levels.The NF-kB p50 and p65 subunits were moderately to strongly expressed in phagocytic macrophages in MS lesions .	directly or indirectly regulate the expression of MHC class I and class II genes	11571785	Details
IRF1	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	In microglial cells localized in normal control white matter, the IRF1 was expressed at weak to moderate levels.The IRF1 was moderately to strongly expressed in phagocytic macrophages in MS lesions .	directly or indirectly regulate the expression of MHC class I and class II genes	11571785	Details
STAT1	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	In microglial cells localized in normal control white matter, the STAT1 was expressed at weak to moderate levels.The STAT1 was moderately to strongly expressed in phagocytic macrophages in MS lesions .	directly or indirectly regulate the expression of MHC class I and class II genes	11571785	Details
CREB1	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	In microglial cells localized in normal control white matter, the CREB1 was expressed at weak to moderate levels.The CREB1 was moderately to strongly expressed in phagocytic macrophages in MS lesions .	directly or indirectly regulate the expression of MHC class I and class II genes	11571785	Details
USF1	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	In microglial cells localized in normal control white matter, the USF1 was expressed at weak to moderate levels.The USF1 was moderately to strongly expressed in phagocytic macrophages in MS lesions .	directly or indirectly regulate the expression of MHC class I and class II genes	11571785	Details
USF2	MS	immunohistochemical	white matter (NAWM)	up-regulation	Disease risk	In microglial cells localized in normal control white matter, the USF2 was expressed at weak to moderate levels.The USF2 was moderately to strongly expressed in phagocytic macrophages in MS lesions .	directly or indirectly regulate the expression of MHC class I and class II genes	11571785	Details
Cd163	EAE	immunohistochemical	lumbar spinal cord (LSC)	up-regulation	Disease risk	A significant up-regulation of CD163 was observed at 11 DPI.	N/A	27846891	Details
Cnp	EAE	immunohistochemical	lumbar spinal cord (LSC)	up-regulation	Disease risk	A significant up-regulation of CNPase was observed at 11 DPI.	N/A	27846891	Details
CD44	EAE	immunohistochemical	lumbar spinal cord (LSC)	up-regulation	Disease risk	A significant up-regulation of CD44 was observed at 11 DPI.	N/A	27846891	Details
Cd86	EAE	immunohistochemical	lumbar spinal cord (LSC)	up-regulation	Disease risk	A significant up-regulation of CD86-IR areas was observed at 11 DPI.	N/A	27846891	Details
Csf1	EAE	immunohistochemical	plasma	N/A	Disease risk	In plasma, CSF1 was significantly up-regulated only at 1 DPI, then continuously decreased till the last time point studied, 18 DPI.	N/A	27846891	Details
Csf1	EAE	immunohistochemical	CSF	N/A	Disease risk	In CSF ,CSF1 level started to decrease at 1 DPI, becoming significant at 11 and 18 DPI.	N/A	27846891	Details
Csf1	EAE	immunohistochemical	tissue	N/A	Disease risk	CSF1-IR in the tissue also increased starting from 1 DPI, then decreased at 5 and 8 DPI ultimately reaching the highest immunoreactivity at 11 DPI .	N/A	27846891	Details
Slc1a2	EAE	immunoblotting	forebrain	up-regulation	Disease risk	Densitometric analysis showed approximately 40% enhancement of protein in EAE rat forebrain relative to control animals in this early phase of disease.	The beneficial effects of glutamate receptors antagonists are strongly suggestive of involvement of glutamatergic receptor-mediated excitotoxicity in the pathogenesis of the disease.The key role in limiting the glutamatergic activity occurs by regulation of the level of extracellular glutamate by GluTs.	18572325	Details
Mog	EAE	enzyme-linked immunosorbent assay	serum and CSF	up-regulation	Disease risk	Sick rats displayed higher levels of anti-MOG IgG, IgG1, IgG2b and IgG2c at the onset of disease in both crosses. During the later phase of EAE, the anti-MOG IgG1 response became higher in healthy rats, whereas total IgG and IgG2b levels remained higher in affected rats compared with healthy rats.	N/A	23784360	Details
A2M	MS	nephelometry	serum	no difference	Disease risk	No difference was observed for the A2M levels between both groups.	Several biological functions have been described for A2M.The structure of the protein suggests a function as protein inhibitor.Furthermore, A2M binds to cytokines and seems to inactivate at least some of themThe protein also enhances antigen-driven immune responses by capturing antigen for presentation.	11498265	Details
LEP	MS	ELISA	serum	no difference	Disease risk	Leptin levels did not show significant differences between studied groups.	MS is mainly considered a Th1-mediated inflammatory disease,although recent studies postulate a vital role for helper T cells-17 (Th17 cells) in the pathogenesis of the disease .Therefore, the pathogenesis of MS is influenced by factors that affect the deviation of nave CD4+ Th cells towards Th1 or Th17 cells.Among different factors, the effects of adipokines such as adiponectin and leptin on Th cell deviation have recently drawn much attention.	30219158	Details
ADIPOQ	MS	ELISA	serum	down-regulation	Disease risk	Adiponectin levels were significantly higher in healthy controls compared to patients.	MS is mainly considered a Th1-mediated inflammatory disease,although recent studies postulate a vital role for helper T cells-17 (Th17 cells) in the pathogenesis of the disease .Therefore, the pathogenesis of MS is influenced by factors that affect the deviation of nave CD4+ Th cells towards Th1 or Th17 cells.Among different factors, the effects of adipokines such as adiponectin and leptin on Th cell deviation have recently drawn much attention.	30219158	Details
CDH11	MS	ELISA	serum	no difference	Phenotypic risk	The frequency of CSF IgG abnormality did not differ significantly between RRMS and SPMS.	N/A	24736746	Details
KIF5A	MS	ELISA	CSF	up-regulation	Disease risk	CSF KIF5A is elevated in MS CSF compared with non-inflammatory neurological disease control.	Both hypo- and hyper- phosphorylation of NFs within axons are recognised as pathological hallmarks of MS and it is believed dysregulated axonal transport could be a catalyst for aberrant protein phosphorylation and accumulation.The majority of anterograde axonal transport is governed by kinesin superfamily motor proteins (KIFs). KIF5A is the main kinesin subtype involved in anterograde transport of phosphorylated NFs.	33484325	Details
KIF5A	MS	ELISA	CSF	up-regulation	Phenotypic risk	CSF KIF5A expression is significantly elevated in progressive MS compared with CIS and RRMS.	Both hypo- and hyper- phosphorylation of NFs within axons are recognised as pathological hallmarks of MS and it is believed dysregulated axonal transport could be a catalyst for aberrant protein phosphorylation and accumulation.The majority of anterograde axonal transport is governed by kinesin superfamily motor proteins (KIFs). KIF5A is the main kinesin subtype involved in anterograde transport of phosphorylated NFs.	33484325	Details
Rasd1	EAE	immunoblot analysis	brain tissues	up-regulation	Disease risk	It was found that Dexras 1 protein was significantly increased in the onset of EAE and the processing development of EAE.	Dexras-1 mediates the effects of NO in the nervous system.	20084551	Details
HLA-G	MS	ELISA	CSF samples	down-regulation	Phenotypic risk	A significant increase was found for sHLA-G levels detected in CSF samples from RR-MS patients with MRI inactivity compared with MRI active patients.	A growing body of evidence has indicated a possible involvement of HLA (Human Leukocyte Antigen)-G antigens in MS where this molecule seems to exhibit antinflammatory properties.HLA-G is characterized by tolerogenic functions, inducing apoptosis of activated CD8+ T cells , acting on T regulatory cells , modulating the activity of natural killer cells and of dendritic cells and blocking allo-cytotoxic T lymphocyte response.These immuno-regulatory functions are mediated by the interaction of HLA-G molecules with specific inhibitory receptors.HLA-G is currently believed to play a tolerogenic role in the regulation of MS autoimmunity.	22922127	Details
NFKB1	MS	flow cytometry	PBMC	down-regulation	Disease risk	We found that nave CD4 cells from patients with MS exhibit significantly higher phospho-p65 NFκB than those from age-matched healthy control donors .	NFκB was one of the first transcription factors identified and is a central regulator of inflammation.	26062845	Details
Ifng	EAE	ELISA	optic nerve	up-regulation	Disease risk	The overall result demonstrates a significant increase in the expression of inflammatory cytokines in the optic nerve of the EAE mouse.	IFN-gamma may aggravate inflammatory injury during the peak stage of optic neuritis.	20428790	Details
Il17a	EAE	ELISA	optic nerve	up-regulation	Disease risk	The overall result demonstrates a significant increase in the expression of inflammatory cytokines in the optic nerve of the EAE mouse.	IL-17 may mediate inflammatory pathogenicity at the early stage of optic neuritis.	20428790	Details
Il4	EAE	ELISA	optic nerve	up-regulation	Disease risk	The overall result demonstrates a significant increase in the expression of inflammatory cytokines in the optic nerve of the EAE mouse.	N/A	20428790	Details
MAP2	MS	Immunocytochemistry	sections of the brains	up-regulation	Disease risk	By immunocytochemistry using a series of monoclonal antibodies specific for MAP-2+13, we determined that MAP-2+13 expression was up-regulated in all 31 lesions from 10 different MS brains. MAP-2+13 was expressed in regenerating oligodendrocytes associated with demyelinated lesions, with the highest counts found in regions of extensive remyelination.	MAP-2 is a family of heat-stable microtubule-associated proteins developmentally expressed in the nervous system. MAP-2 reduces the concentration of tubulin required to form microtubules and is involved in regulating cytoskeletal dynamics, dendritic elongation, and neuronal plasticity.	10582615	Details
BCL2	MS	Immunocytochemistry	autopsy tissues	down-regulation	Phenotypic risk	Bcl-2 is expressed by T lymphocytes in MS plaques.Patients with chronic progressive MS have a higher proportion of bcl-2 expressing T cells than patients with relapsing remitting disease.Highest numbers of bcl-2-positive T lymphocytes were found in remyelinating and demyelinated lesions, whereas active demyelinating lesions revealed lower numbers.	Studies in animal models of MS suggest that apoptosis of T cells is the main factor terminating inflammation.The process of apoptosis itself is regulated by a range of pro- and anti-apoptotic proteins.The bcl-2 gene family is an important member of these proteins.	9717185	Details
HLA-G	MS	ELISA	serum	No significance	Disease risk	We did not detect significantly different serum level of sHLA-G between groups.	Multiple sclerosis (MS) is the most common chronic inflammatory demyelinating disorder of central nervous system in young population. It has been suggested that major histocompatibility complex (MHC) on chromosome 6p21 is the strongest genome-wide MS susceptibility factor. HLA-G is a non-classical HLA class I with limited polymorphisms.	29924453	Details
CCL20	MS	ELISA	serum	up-regulation	Disease risk	The mean serum levels of CCL20 in the MS group were significantly higher than healthy group.	The migration of auto reactive T cells from circulation into the CNS across the (BBB) is a crucial step in the development of pathological lesions in MS, the recruitment of inflammatory cells is controlled by chemokines.CCL20–CCR6 interaction participates in BBB disruption and the subsequent transmigration of pathogenic T cell into the CNS.Moreover, secretion of IL-17 from circulating Th17 cells amplifies the proinflammatory response by enhancing CCL20 transcription via NFkB signaling.	30399422	Details
IL2RA	MS	Quantikine ELISA	plasma	No significance	Disease risk	No significant differences were seen in the sCD25 levels between MS patients or MS subtypes and HCs.	The soluble form of CD25 (sCD25) may function as an antagonist for IL-2 .However, sCD25 may also facilitate T cell activation and increased T cell proliferation has been observed after addition of sCD25.By sCD25 binding of IL-2 the IL-2 promoted activation induced cell death (AICD) could be prevented as well as the negative feedback inhibition of IL-2 itself .Furthermore, an increase in sCD25 levels enhanced the severity of experimental autoimmune encephalomyelitis (EAE).This occurred in association with increased antigen-specific T-cell expression of IL-17A in the periphery and increased numbers of both interferon-gamma (IFNγ) and IL-17 producing CD4+ T cells in the CNS.	28511943	Details
Cnr1	EAE	isotope dilution-liquid chromatography/mass spectrometry (LC-MS)	brain	down-regulation	Disease risk	We recorded a marked reduction of both anandamide and 2-arachidonoylglycerol in motor related regions (striatum, midbrain) but also in other regions such as the brainstem, diencephalon, hippocampus, limbic forebrain, and cerebral cortex.	a reduction of CB1 receptor binding and mRNA levels, mainly in the basal ganglia , and a region-dependent down-regulation of endocannabinoid transmission in EAE rats	16242629	Details
Eif2s1	EAE	immunoblotting	brain	up-regulation	Disease risk	We observed PERK activation, as demonstrated by increased eIF2α phosphorylation.	PERK activation	25113558	Details
Stat3	EAE	immunoblotting	brain	up-regulation	Disease risk	increased activation-associated phosphorylation of STAT3	the presence of ER stress in the CNS during EAE	25113558	Details
NPY	MS	ELISA	peripheral blood	up-regulation	Disease risk	Serum NPY level was significantly higher in RR-MS and PR-MS than in healthy controls (p < 0.001 and p = 0.001, respectively), and it was lower in patients with mild or moderate/severe disease than in healthy controls (p < 0.001)	N/A	37013432	Details
TACR1	MS	ELISA	peripheral blood	down-regulation	Disease risk	Significant inverse correlations were found between SP level and MS disease duration (r = -0.279, p = 0.022) and duration of current DMT	N/A	37013432	Details
aCGRP	MS	ELISA	peripheral blood	up-regulation	Disease risk	Serum aCGRP level was higher in PR-MS compared to RR-MS (p = 0.007) and healthy controls (p = 0.001), and it positively correlated with EDSS	N/A	37013432	Details
Tspo	EAE	Immunohistochemistry	brain and spinal cord	down-regulation	Disease risk	This decrease in astrogliosis was also witnessed in the lessening of severity of EAE clinical scoring, indicating an in vivo functional role for TSPO in suppressing EAE.	TSPOFlox/Flox/hGFAPcre mice showed highly down regulated TPSO expression, with minimal expression of TPSO in the central canal	26925573	Details
S1pr1	EAE	Flow cytometric analysis	cell	up-regulation	Disease risk	Mutant mice harboring an S1pr1 gene encoding phosphorylation-deficient receptors (S1P1(S5A)) developed severe experimental autoimmune encephalomyelitis (EAE) due to autoimmunity mediated by interleukin 17 (IL-17)–producing helper T cells (TH17 cells) in the peripheral immune and nervous system	S1P1 directly activated the Jak-STAT3 signal-transduction pathway via IL-6. Impaired S1P1 phosphorylation enhances TH17 polarization and exacerbates autoimmune neuroinflammation	24076635	Details
Ikbkb	EAE	Immunoblot analysis	brain and spinal cord	down-regulation	Disease risk	CNS-restricted ablation of ‘upstream’ NF-jB activators NEMO or IKK2 but not IKK1 ameliorated disease pathology in a mouse model of multiple sclerosis	CNS-restricted ablation	16892069	Details
Chuk	EAE	Immunoblot analysis	brain and spinal cord	N/A	Negative	CNS-restricted ablation of ‘upstream’ NF-jB activators NEMO or IKK2 but not IKK2 ameliorated disease pathology in a mouse model of multiple sclerosis	N/A	16892069	Details
Ikbkg	EAE	Immunoblot analysis	brain and spinal cord	down-regulation	Disease risk	CNS-restricted ablation of ‘upstream’ NF-jB activators NEMO or IKK2 but not IKK3 ameliorated disease pathology in a mouse model of multiple sclerosis	CNS-restricted ablation	16892069	Details
Mst1r	EAE	Immunoblot analysis	Brain tissue	down-regulation	Disease risk	Neurological disease in RON-deficient animals showed a more rapid onset with overall worsened severity, together with exacerbated demyelination, axonal injury, and neuroinflammation after EAE induction	RON Receptor Expression Is Reduced	15929040	Details
MST1R	MS	Immunoblot analysis	Brain tissue	down-regulation	Disease risk	RON mRNA and protein abundance in the CNS were diminished in both MS patients and the MS animal model, experimental autoimmune encephalomyelitis (EAE)	RON Receptor Expression Is Reduced	15929040	Details
APOE	MS	Immunohistochemistry	N/A	up-regulation	Disease risk	ApoE immunoreactivity was increased in demyelinated areas compared with control white matter.	apoE is involved in the trafficking of lipid in MS	10888365	Details
BIRC5	MS	WB,ELISA	whole blood	up-regulation	Disease risk	The mRNA of survivin was 2-folds upregulated in the CD4+ T cells from MS patients in comparison to the healthy controls (P= 0.0053). Serum level of survivin was higher in patients than controls. There was statistically significant downregulation of miR-485 (P= 0.001) and miR-708 (P= 0.011) in CD4+ T cells of patients compared with controls. The miR-485 downregulation had statistically significant correlation with the mRNA expression and serum level of survivin.	persistent inflammatory condition	32599467	Details
HLA-DRB1	MS	ELISA	cortical gray matter	up-regulation	Disease risk	Analysis of gray matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression.	Our data indicate that increased HLA-DRB1 and -DRB5 expression in the brain ofpatients with MS may be an important factor in how the HLA-DR15 haplotype contributes to MS pathomechanisms in the target organ.	31882398	Details
MIR146A	MS	ELISA	peripheral blood	up-regulation	Disease risk	the genotype (GC+CC) of rs2910164 predicted relapse compared with the GG genotype (HR=2.09 (95% CI 1.42, 3.06), p=0.0001), as well as a near-significant (p=0.07) association with MS conversion risk	relative excess risk due to interaction	29127522	Details
TNF	MS	WB	peripheral blood	up-regulation	Disease risk	This finding represents a novel immunomodulatory mechanism of IFN-b: inhibition of TLR9 processing. This results in decreased activation of pDCs by viral pathogens and, thus, may affect the frequency of MS exacerbations.	inhibition of TLR9 processing	21061396	Details
IL6	MS	WB	peripheral blood	up-regulation	Disease risk	This finding represents a novel immunomodulatory mechanism of IFN-b: inhibition of TLR10 processing. This results in decreased activation of pDCs by viral pathogens and, thus, may affect the frequency of MS exacerbations.	inhibition of TLR10 processing	21061396	Details
TLR9	MS	WB	peripheral blood	up-regulation	Disease risk	This finding represents a novel immunomodulatory mechanism of IFN-b: inhibition of TLR11 processing. This results in decreased activation of pDCs by viral pathogens and, thus, may affect the frequency of MS exacerbations.	inhibition of TLR11 processing	21061396	Details
IFNA2	MS	WB	peripheral blood	up-regulation	Disease risk	This finding represents a novel immunomodulatory mechanism of IFN-b: inhibition of TLR12 processing. This results in decreased activation of pDCs by viral pathogens and, thus, may affect the frequency of MS exacerbations.	inhibition of TLR12 processing	21061396	Details
CLEC16A	MS	WB	peripheral blood	up-regulation	Disease risk	CLEC16A participates in the BCR-dependent HLA-II pathway in human B cells and that this regulation is impaired during MS disease onset. .	The abundance of CLIP already on naive B cells of MS patients may point to a chronically induced stage and a new mechanism underlying B cell–mediated autoimmune diseases such as MS	32641384	Details
Dock9	EAE	ELISA、Immunofluorescence	retina，optic nerves	N/A	Disease risk	the disease severity was reduced in DOCK10-/- mice, but not in DOCK9-/- or DOCK11-/-	N/A	32241915	Details
Dock11	EAE	ELISA、Immunofluorescence	retina，optic nerves	N/A	Disease risk	the disease severity was reduced in DOCK10-/- mice, but not in DOCK9-/- or DOCK11-/-	N/A	32241915	Details
Dock10	EAE	ELISA、Immunofluorescence	retina，optic nerves	down-regulation	Disease risk	EAE severity was ameliorated in DOCK10-/- mice	innate immunity and neuroinflammation	32241915	Details
Cfh	EAE	IFHC	liver and brain	down-regulation	Disease risk	The expression of CFH gene in brain had a significant decrease in acute and chronic phases compared to healthy mice	immune response	30972735	Details
Mir146	EAE	IFHC	liver and brain	down-regulation	Disease risk	The expression of CFH gene in brain had a significant decrease in acute and chronic phases compared to healthy mice	immune response	30972735	Details
Per2	EAE	radioimmunoassay	peripheral blood	up-regulation	Disease risk	significant variability associated with Per2 rhythmic expression.	disturbances in clock-regulated rhythms	22209286	Details
Mbp	EAE	Gel electrophoresis and immunoblotting	peripheral blood	down-regulation	Disease risk	A chimeric protein such as MBP-PE40 presents a novel prototype of chimeric proteins, composed of antigen/peptide-toxin, that could prove to be an efficient and specific immunotherapeutic agent for autoimmune diseases in which a known antigen is involved	cytotoxic to various anti-MBP T cells	10424450	Details
Rnf128	EAE	WB	CNS tissues	down-regulation	Disease risk	suppressed PLP-induced T cell proliferation by enhancing T cell expression of GRAIL as GRAIL downregulation restored T cell proliferation	HINT1/Hsp70 treatment generated regulatory NK cells characterized by expression of GRAIL.	31362466	Details
HSPA4	MS	WB	Whole blood	up-regulation	Disease risk	indicating animplication of the G allele ofHSP70-2 gene polymorphism in the development ofMS.	an inducible chaperon induced under stress conditions	24485944	Details
HSPA1B	MS	WB	Whole blood	negative	Disease risk	HSP70-2 does not seem to be central in the protection ofPBMCs	HSP70-2 protein expression and the production of intracellular reactive oxygen species were assessed	31720998	Details
PLP1	MS	IFHC	serum	positive	Disease risk	PLP58-74 can stimulate CD4+ T cells and humoral immunity. Therefore it seems that the epitopes of some microorganisms mimicking PLP such as PLP58-74 might have a potential role in the initiation of MS.	self-antigens expressed	27917626	Details
SERPINA3	MS	ELISA	CSF	up-regulation	Disease risk	CSF SERPINA3 and S100A4 levels were significantly increased in the whole group of patients with MS compared with NINCs.	N/A	33436375	Details
S100A4	MS	ELISA	CSF	up-regulation	Disease risk	CSF SERPINA3 and S100A4 levels were significantly increased in the whole group of patients with MS compared with NINCs.	N/A	33436375	Details
Serpina3n	EAE	IFHC	forebrain	up-regulation	Disease risk	Reveal a Primarily Neuronal Expression ofSerpina3n andS100A4 During EAE	N/A	33436375	Details
S100a4	EAE	IFHC	forebrain	up-regulation	Disease risk	Reveal a Primarily Neuronal Expression ofSerpina3n andS100A4 During EAE	N/A	33436375	Details
Mbp	EAE	Immunohistochemistry	spinal cord	up-regulation	Disease risk	combined therapy of vitamins A and C effectively protect myelin damage in EAE model via increasing MBP level and BDNF as a crucial protein in myelin repair	N/A	35072933	Details
Bdnf	EAE	Immunohistochemistry	spinal cord	up-regulation	Disease risk	combined therapy of vitamins A and C effectively protect myelin damage in EAE model via increasing MBP level and BDNF as a crucial protein in myelin repair	N/A	35072933	Details
CXCL12	MS	ELISA	peripheral blood	up-regulation	Disease risk	we detected increased protein CXCL12 serum levels in both individuals with RRMS and SPMS compared to controls	N/A	27519689	Details
Rae1	EAE	Flow cytometry and cell sorting	cell	up-regulation	Disease risk	RAE-1 expression is correlated with the proliferative state of microglial cells but not with their phenotypic M1/M2 orientation.	N/A	27444966	Details
Atp2b2	EAE	IFHC;WB	spinal cord	down-regulation	Disease risk	Transcript and protein levels of plasma membrane Ca2+ ATPase 2 (PMCA2) were dramatically decreased coincident with the onset of clinical symp- toms	perturbations in Ca2+ balance and neurotransmitter exocytosis may partially underlie aberrant neuronal function and communication at onset of symptoms. Altered mitochondrial function and impulse conduction may exacerbate neurological decits at subsequent disease stages.	12538406	Details
Mir23b	EAE	immunohistochemistry;WB;ELISA	Brain and lumbar spinal cords	down-regulation	Disease risk	miR-23b reduced the severity of EAE by inhibiting the migration of pathogenic T cells to the CNS rather than diminishing the encephalitogenesis of T cells.	inhibiting the migration of pathogenic T cells to the CNS	29275848	Details
Mapk14	EAE	Western blot	spinal cord	up-regulation	Disease risk	oral administration of a highly specific p38 inhibitor (UR5269) to WT mice at the onset ofEAE markedly suppressed the progression of EAE compared with a vehicle group.	through IL-17 induction.	22637476	Details
CLDN11	MS	ELISA	peripheral blood	N/A	Disease risk	Detection of proteins by ELISA showed no significant differences in plasma concentration of MMP-2 and Claaudin-11 between two groups	Leukocytes penetration into the blood-brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics	26768647	Details
MMP2	MS	ELISA	peripheral blood	N/A	Disease risk	Detection of proteins by ELISA showed no significant differences in plasma concentration of MMP-2 and Claaudin-11 between two groups	Leukocytes penetration into the blood-brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics	26768647	Details
TGFB1	MS	ELISA	peripheral blood	up-regulation	Disease risk	the plasma levels of TGF-β1、TGF-β2 and TGF-β3 were significantly elevated in MS patients	Leukocytes penetration into the blood-brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics	26768647	Details
TGFB2	MS	ELISA	peripheral blood	up-regulation	Disease risk	the plasma levels of TGF-β1、TGF-β2 and TGF-β3 were significantly elevated in MS patients	Leukocytes penetration into the blood-brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics	26768647	Details
TGFB3	MS	ELISA	peripheral blood	up-regulation	Disease risk	the plasma levels of TGF-β1、TGF-β2 and TGF-β3 were significantly elevated in MS patients	Leukocytes penetration into the blood-brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics	26768647	Details
LAG3	MS	Elisa	peripheral blood	down-regulation	Disease risk	Surface and intracellular LAG-3 protein is diminished after TCR stimulation in RRMS	The co-inhibitory receptor lymphocyte activation gene 3 (LAG-3) is an immune checkpoint	35022272	Details
IL23A	MS	Elisa	peripheral blood	up-regulation	Disease risk	IL-23 expression is eleveted in monocyte-derived DCs from MS patients both at the protein and mRNA levels	Our results demonstrate that an abnormal Th1 bias in DCs from MS patients related to IL-23 exists, and that antisense oligonucleotides specific to IL-23 can be used for immune modulation by targeting DC gene expression	16751425	Details
Csf1	EAE	Western Blotting	spinal cord	up-regulation	Disease risk	CSF-1 protein was also detected in the central nervous system at the height of clinical disease	within the CNS, the production of factors that recruit macrophages from the periphery into the spinal cord and lead to the expansion and activation of these cells are an important component of the encephalitogenic process.	8450228	Details
Csf1r	EAE	Western Blotting	spinal cord	up-regulation	Disease risk	Unlike CSF-1 message levels, c-fms expression remained elevated after resolution of the acute disease episode	within the CNS, the production of factors that recruit macrophages from the periphery into the spinal cord and lead to the expansion and activation of these cells are an important component of the encephalitogenic process.	8450228	Details
Ccl2	EAE	Western Blotting	spinal cord	up-regulation	Disease risk	Macrophage chemotactic factor-1 protein was demonstrated by Western blot in the central nervous system at the height of clinical disease	within the CNS, the production of factors that recruit macrophages from the periphery into the spinal cord and lead to the expansion and activation of these cells are an important component of the encephalitogenic process.	8450228	Details
Il10	EAE	Cytokine analysis	spleen	up-regulation	Disease risk	These mice were found to express large numbers of IL-10-secreting splenocytes as early as 4 weeks of age	Further investigation of this phenomenon, particularly of the failure to develop spontaneous EAE early, is reported in the present paper	33565605	Details
IL1B	MS	ELISA	peripheral blood	up-regulation	Disease risk	we show that families that are characterized by high IL-1beta over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p=0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio	These studies indicate thatthe balance between IL-1hand IL-1Ra production mightbe of importance for MS, rather than the absolute level ofeach cytokine alone	12020968	Details
IL1RN	MS	ELISA	peripheral blood	up-regulation	Disease risk	we show that families that are characterized by high IL-1beta over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p=0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio	These studies indicate thatthe balance between IL-1hand IL-1Ra production mightbe of importance for MS, rather than the absolute level ofeach cytokine alone	12020968	Details
Hmox1	EAE	ABC	brain	up-regulation	Disease risk	The results showed that the levels of HO-1 mRNA and its protein expression were very low in the brains of the control group, whereas they were enhanced gradually with pathological course in the brain and onsets of symptoms, signs of EAE.The levels of HO-1 mRNA and its protein expression were lowered gradually on day 21, which were in parallel with the severities of symptoms and signs of EAE	Antioxidant effect	15497037	Details
RUNX1	MS	Elisa	peripheral blood	down-regulation	Disease risk	the protein levels of RUNX1, MAP2, NGF, BDNF and IL-10 were significantly decreased in MS patients compared to healthy controls	Altogether, this study suggests the implication of the RUNXOR–RUNX1 axis in MS development, progression, and increased MS-related disability	36754216	Details
MAP2	MS	Elisa	peripheral blood	down-regulation	Disease risk	the protein levels of RUNX1, MAP2, NGF, BDNF and IL-10 were significantly decreased in MS patients compared to healthy controls	Altogether, this study suggests the implication of the RUNXOR–RUNX1 axis in MS development, progression, and increased MS-related disability	36754216	Details
NGF	MS	Elisa	peripheral blood	down-regulation	Disease risk	the protein levels of RUNX1, MAP2, NGF, BDNF and IL-10 were significantly decreased in MS patients compared to healthy controls	Altogether, this study suggests the implication of the RUNXOR–RUNX1 axis in MS development, progression, and increased MS-related disability	36754216	Details
BDNF	MS	Elisa	peripheral blood	down-regulation	Disease risk	the protein levels of RUNX1, MAP2, NGF, BDNF and IL-10 were significantly decreased in MS patients compared to healthy controls	Altogether, this study suggests the implication of the RUNXOR–RUNX1 axis in MS development, progression, and increased MS-related disability	36754216	Details
IL10	MS	Elisa	peripheral blood	down-regulation	Disease risk	the protein levels of RUNX1, MAP2, NGF, BDNF and IL-10 were significantly decreased in MS patients compared to healthy controls	Altogether, this study suggests the implication of the RUNXOR–RUNX1 axis in MS development, progression, and increased MS-related disability	36754216	Details
NDFIP1	MS	Western blot	peripheral blood	down-regulation	Disease risk	the protective genotype induced a reduction to half the protein levels compared to major-allele carriers in healthy controls	NDFIP1 shows interesting immune functions and is involved in the development of the central nervous system	34725369	Details
Cxcl13	EAE、TMEV-IDD	ELISA	spinal cord	up-regulation	Phenotypic risk	CXCL13 protein levels were significantly higher in TMEV-IDD mice compared to R-EAE and sham mice	Active cycling between demyelination/remyelination and axonal regeneration in the spinal cord of R-EAE mice but not in the spinal cord of mice in the later stage of TMEV-IDD.	31118079	Details
Chil4	EAE、TMEV-IDD	ELISA	spinal cord	up-regulation	Phenotypic risk	ELISA for protein of Chi3l4 showed increased expression in R-EAE mice	A gene set enriched in processes related to adaptive immune responses, particularly T cell recruitment, activation, and differentiation.	31118079	Details
Ighg1	EAE、TMEV-IDD	Protein measurements by Luminex	spinal cord	up-regulation	Phenotypic risk	Levels of IgG1 protein in the spinal cord were significantly higher in TMEV-IDD mice compared with R-EAE mice	Ig production capacities can be associated with the stage of the disease	31118079	Details
Bdnf	EAE	ELISA	Dorsal root ganglia (DRG)	up-regulation	Disease risk	At 12 dpi in the EAE DRG, BDNF levels were significantly increased compared to AC day 12 DRG,	BDNF may play a significant role in the induction and progression of neuronal and oligodendrocyte damage.	22050733	Details
Bdnf	EAE	ELISA	spinal cord	up-regulation	Disease risk	Experimental autoimmune encephalomyelitis animals showed a significant increase in BDNF expression in the caudal spinal cord	This corroborates previous studies showing anterograde transport of BDNF along microtubules via transport vesicles	22050733	Details
Xiap	EAE	Western Blotting	brain	up-regulation	Disease risk	High levels of protein expression were detected in the brain	Our results demonstrate that compared to WT-littermates, ubXIAP mice display an earlier EAE onset andelevated clinical scores, suggesting that increased XIAP ex-pression renders effector T cells more resistant to apoptoticstimuli	18687476	Details
Abl2	EAE	Western Blotting	brain	up-regulation	Disease risk	Arg is highly expressed in mouse brain and moderately expressed in spleen	Abl2/Arg a candidate gene for EAE.	29550852	Details
Abl2	EAE	Western Blotting	spleen	up-regulation	Disease risk	Arg is highly expressed in mouse brain and moderately expressed in spleen	Abl2/Arg a candidate gene for EAE.	29550852	Details
Sult1a1	EAE	TaqMan PCR	spinal cord	up-regulation	Disease risk	The difference in protein expression was not as evident as for mRNA expression, but thick astrocytic processes and white matter astrocytes were more easily detected in EAE mice than in control mice in which most fine astrocytic process appeared weakly labeled	astrocytes may have not only altered sex steroid synthesis but also higher estrogen conjugation activity, both potentially leading to lower intracellular concentrations active estrogen	26141748	Details
Il7	EAE	ELISA	brain	up-regulation	Disease risk	We found that high levels of serum IL-7 predict clinical responsiveness in MS patients undergoing IFN-β therapy.	IL-7Rα–specific antibody reduced nave and effector memory T cells	21795588	Details
Cx3cl1	EAE	ELISA	spinal cord	up-regulation	Disease risk	Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG) and spinal cord (SC) 12 days after EAE induction compared to controls.	we conclude that the changes in CX3CL1 and CX3CR1 expression levels are the direct result of activation of the immune response by CNS-myelin-specific antigens such as MBP	24175290	Details
Cx3cr1	EAE	ELISA	spinal cord	up-regulation	Disease risk	Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG) and spinal cord (SC) 12 days after EAE induction compared to controls.	we conclude that the changes in CX3CL1 and CX3CR1 expression levels are the direct result of activation of the immune response by CNS-myelin-specific antigens such as MBP	24175290	Details
Cx3cl1	EAE	ELISA	Dorsal root ganglia (DRG)	up-regulation	Disease risk	Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG) and spinal cord (SC) 12 days after EAE induction compared to controls.	we conclude that the changes in CX3CL1 and CX3CR1 expression levels are the direct result of activation of the immune response by CNS-myelin-specific antigens such as MBP	24175290	Details
Cx3cr1	EAE	ELISA	Dorsal root ganglia (DRG)	up-regulation	Disease risk	Results revealed significant increases in mRNA and the protein expression of CX3CL1 and CX3CR1 in the dorsal root ganglia (DRG) and spinal cord (SC) 12 days after EAE induction compared to controls.	we conclude that the changes in CX3CL1 and CX3CR1 expression levels are the direct result of activation of the immune response by CNS-myelin-specific antigens such as MBP	24175290	Details
Nfe2l2	EAE	Western Blotting	spinal cord	up-regulation	Disease risk	The relevance of our findings isunderlined by studies on multiple sclerosis autopsy tissue showingthat neuronal Nrf2 is also activated during the natural course ofmultiple sclerosis, similar to our findings in untreated EAE	Nrf2-mediated neuroprotection may not only be directly mediated,but critically involves effects via astrocytes	21354971	Details
IL17A	MS	ELISA	peripheral blood	up-regulation	Disease risk	These results indicated higher levels of IL-17 in MS patients that may be influenced by disease patterns, medication and gender. No association was observed between investigated SNPs and MS.	Interleukin (IL)-17/IL-23 axis performs a prominent role in the pathogenesis of several autoimmune disorders.	28717429	Details
IL18	MS	ELISA	peripheral blood	up-regulation	Disease risk	In this study, we showed the significant higher IL-18 serum level and significant different frequencies of two polymorphisms of IL-18 in MS patients. These results show the important roles of IL-18 in MS pathogenesis. However, more studies are needed to verify our results in larger sample size.	Multiple sclerosis (MS) is a chronic demyelinating disorder of central nervous system. Although the definite pathogenesis of MS has not been understood, crucial role of environmental and genetic risk factors has been proposed.	31736573	Details
CD14	MS	ELISA	peripheral blood	up-regulation	Phenotypic risk	In summary, we conclude that CD14-159 and -260 polymorphisms are associated with the risk of MS in Iranian population and affects CD14 promoter activity, thereby regulating CD14 expression.	Besides the central role of the adaptive immune system, a disturbance of innate immune system is also suggested to be involved in the pathogenesis of multiple sclerosis (MS).	27819517	Details
Ccr2	EAE	real-time PCR	serum	down-regulation	Disease risk	Selective depletion of this specific monocyte subpopulation through engagement of CCR2 strongly reduced central nervous system autoimmunity.	Collectively, these data indicate a disease-promoting role of CCR2+Ly-6Chi monocytes during autoimmune inflammation of the central nervous system.	19531531	Details
IL6	MS	ELISA	serum	up-regulation	Disease risk	IL6 (p \ 0.01, Fig. 1c) were found to increase with lower miR26a expression in PBLs of patients with RRMS or patients with relapsing MS	Using the EAE model system, in vivo silencing of miR26a was found to result in increased expression of Th17-related cytokines and increased severity of EAE, while overexpression of miR26a was found to result in reduced expression of Th17- related cytokines and a milder form of EAE.	25362566	Details
FOXP3	MS	ELISA	serum	down-regulation	Disease risk	the Foxp3 gene (p \ 0.05, Fig. 1b) showed the same pattern with miR26a. Using	Using the EAE model system, in vivo silencing of miR26a was found to result in increased expression of Th17-related cytokines and increased severity of EAE, while overexpression of miR26a was found to result in reduced expression of Th17- related cytokines and a milder form of EAE.	25362566	Details
Il6	EAE	ELISA	Brain	up-regulation	Disease risk	Brain tissues from EAE mice showed significantly higher expression of RORct (p \ 0.01, Fig. 2a), IL17 (p \ 0.01, Fig. 2a), and IL6 (p \ 0.01, Fig. 2a) mRNA in the acute phase, but significantly lower expression of miR26a (p \ 0.01, Fig. 2b) and Foxp3 (p \ 0.05, Fig. 2a).	As shown in Fig. 4 c through d, IL6 knockdown led to the downregulation of RORct (p \ 0.05, Fig. 4c), IL17 (Fig. 4c, p \ 0.05, and d, p \ 0.01), and IL6 (p \ 0.01, Fig. 4c, d) and to the upregulation of Foxp3 (p \ 0.05, Fig. 4c), results that were similar to those found by using miR26a.	25362566	Details
Il17a	EAE	ELISA	Brain	down-regulation	Disease risk	Brain tissues from EAE mice showed significantly higher expression of RORct (p \ 0.01, Fig. 2a), IL17 (p \ 0.01, Fig. 2a), and IL6 (p \ 0.01, Fig. 2a) mRNA in the acute phase, but significantly lower expression of miR26a (p \ 0.01, Fig. 2b) and Foxp3 (p \ 0.05, Fig. 2a).	As shown in Fig. 4 c through d, IL6 knockdown led to the downregulation of RORct (p \ 0.05, Fig. 4c), IL17 (Fig. 4c, p \ 0.05, and d, p \ 0.01), and IL6 (p \ 0.01, Fig. 4c, d) and to the upregulation of Foxp3 (p \ 0.05, Fig. 4c), results that were similar to those found by using miR27a.	25362566	Details
Rorc	EAE	ELISA	Brain	down-regulation	Disease risk	Brain tissues from EAE mice showed significantly higher expression of RORct (p \ 0.01, Fig. 2a), IL17 (p \ 0.01, Fig. 2a), and IL6 (p \ 0.01, Fig. 2a) mRNA in the acute phase, but significantly lower expression of miR26a (p \ 0.01, Fig. 2b) and Foxp3 (p \ 0.05, Fig. 2a).	As shown in Fig. 4 c through d, IL6 knockdown led to the downregulation of RORct (p \ 0.05, Fig. 4c), IL17 (Fig. 4c, p \ 0.05, and d, p \ 0.01), and IL6 (p \ 0.01, Fig. 4c, d) and to the upregulation of Foxp3 (p \ 0.05, Fig. 4c), results that were similar to those found by using miR28a.	25362566	Details
Foxp3	EAE	ELISA	Brain	down-regulation	Disease risk	Brain tissues from EAE mice showed significantly higher expression of RORct (p \ 0.01, Fig. 2a), IL17 (p \ 0.01, Fig. 2a), and IL6 (p \ 0.01, Fig. 2a) mRNA in the acute phase, but significantly lower expression of miR26a (p \ 0.01, Fig. 2b) and Foxp3 (p \ 0.05, Fig. 2a).	As shown in Fig. 4 c through d, IL6 knockdown led to the downregulation of RORct (p \ 0.05, Fig. 4c), IL17 (Fig. 4c, p \ 0.05, and d, p \ 0.01), and IL6 (p \ 0.01, Fig. 4c, d) and to the upregulation of Foxp3 (p \ 0.05, Fig. 4c), results that were similar to those found by using miR29a.	25362566	Details
Apoe	EAE	ELISA	serum and Spinal cord	down-regulation	Disease risk	apoE deficiency ameliorates EAE course in male but not female mice	As sex hormones modify immunomodulatory apoE functions, they may explain contentious findings.	26669675	Details
Fadd	EAE	ELISA，western blot	peripheral blood	up-regulation	Phenotypic risk	We found that overexpression of the long form of human FLICE-inhibitory protein by retroviral gene transfer of hemopoietic stem cells led to a clinically more severe EAE in these mice compared with control mice receiving the retroviral vector alone.	Subsidence of inflammation and clinical recovery in experimental autoimmune encephalomyelitis (EAE) is postulated to involve apoptosis of inflammatory cells.	12574377	Details
STAT1	MS	ELISA	peripheral blood	up-regulation	Treatment risk	Based on this proof of concept study, we hypothesize that NAb effects can be monitored by evaluation of a single biomarker, pStat1, in either monocytes or T cells by phosphoflow directly after IFN-b administration. The method will significantly reduce cost relative to labor intensive in vitro methods and offers a patient-specific approach to NAb evaluation.	Anti interferon-beta (IFN-b) neutralizing antibodies (NAb) affect efficacy of treatment of multiple sclerosis patients, but exactly when the detrimental effects of NAbs offset therapeutic efficacy is debated. Quantification of intracellular pathway-specific phosphorylation by phospho-specific flow cytometry (phosphoflow) is a promising tool for evaluation of these effects in primary immune cells from treated patients at the single-cell level.	24586361	Details
CXCL10	MS	ELISA	peripheral blood	up-regulation	Disease risk	Circulating MSCs, IP-10 and SDF-1α levels, increased in RRMS patients with clinically active not on DMT and IFN-β therapy reduced circulating MSCs and SDF-1α levels.	Mesenchymal stem cells (MSCs) have the capacity to migrate into the inflammatory regions in response to chemokines such as, IP-10 and SDF-1α and function as anti-inflammatory and immunomodulatory cells	31421626	Details
CXCR4	MS	ELISA	peripheral blood	up-regulation	Disease risk	Circulating MSCs, IP-10 and SDF-1α levels, increased in RRMS patients with clinically active not on DMT and IFN-β therapy reduced circulating MSCs and SDF-1α levels.	Mesenchymal stem cells (MSCs) have the capacity to migrate into the inflammatory regions in response to chemokines such as, IP-10 and SDF-1α and function as anti-inflammatory and immunomodulatory cells	31421626	Details
MAPT	MS	Immunoprecipitation	Brain	up-regulation	Disease risk	Immuno-histochemistry with AT8 and MD3.1 confirmed prior reports of tau accumulation in MS. Although larger studies are required, our data suggest that progressive MS may be considered a secondary tauopathy	Relapsing remitting multiple sclerosis (MS) is an inflammatory demyelinating disorder of the central nervous system that in many cases leads to progressive MS, a neurodegenerative disease.	36221144	Details
SGPL1	MS	Immunoprecipitation，Western blot	peripheral blood	up-regulation	Treatment risk	Among the exclusive binding partners of the risk variant, we describe the novel interaction with sphingosine 1-phosphate lyase (SGPL1)—a key enzyme for the creation of the sphingosine-1 phosphate gradient, which is relevant to the pathogenic process and therapeutic management of MS.	Despite recent progress in the characterization of genetic loci associated with multiple sclerosis (MS) risk, the ubiquitous linkage disequilibrium operating across the genome has stalled efforts to distinguish causative variants from proxy single-nucleotide polymorphisms (SNPs).	26433934	Details
EVI5	MS	Immunoprecipitation，Western blot	peripheral blood	up-regulation	Disease risk	We further show that an exonic SNP associated with risk induces changes in superficial hydrophobicity patterns of the coiled-coil domain of EVI5, which, in turns, affects the EVI5 interactome. Immunoprecipitation of wild-type and mutated EVI5 followed by mass spectrometry generated a roster of disease-specific interactors functionally linked to lipid metabolism.	Despite recent progress in the characterization of genetic loci associated with multiple sclerosis (MS) risk, the ubiquitous linkage disequilibrium operating across the genome has stalled efforts to distinguish causative variants from proxy single-nucleotide polymorphisms (SNPs).	26433934	Details
IL6ST	MS	ELISA	peripheral blood	down-regulation	Treatment risk	During natalizumab treatment we observed a decline in sgp130 and sIL-7Rα levels, while subsequent fingolimod treatment lead to increased sgp130 and sIL-7Rα and decreased sIL-2Rα levels.	Genetic variants within some cytokine receptor genes have been associated with MS susceptibility, including IL7RA and IL2RA.	28941836	Details
STIL	MS	ELISA	peripheral blood	down-regulation	Treatment risk	During natalizumab treatment we observed a decline in sgp130 and sIL-7Rα levels, while subsequent fingolimod treatment lead to increased sgp130 and sIL-7Rα and decreased sIL-2Rα levels.	Genetic variants within some cytokine receptor genes have been associated with MS susceptibility, including IL7RA and IL2RA.	28941836	Details
MMP3	MS	ELISA	Brain	up-regulation	Disease risk	Autopsied brain sections from multiple sclerosis patients containing aggregates of B cells expressed a significantly higher amount of matrix metalloproteinase-3 compared to controls	There has been a growing interest in the presence and role of B cell aggregates within the central nervous system of multiple sclerosis patients.	36389698	Details
HSPA4	MS	ELISA，western blot	PBMC	up-regulation	Disease risk	These results indicate that immune cells from MS patients are more prone to Hsp70 induction under stress conditions, suggesting a possible link between Hsp70 overexpression and development of auto-immunity.	Heat shock protein 70 (Hsp70), a prominent member of the heat shock protein family, is a stress-induced chap-erone, contributing to the ‘‘protein triage’’ mechanism	20806409	Details
MPO	MS	Immunoprecipitation	peripheral blood	up-regulation	Disease risk	This is the first evidence that MPO is present in microgliarmacrophages at MS lesions, that MPO gene expression occurs in microglia and that MPO plays a role in MS pathogenesis as shown by the allelic disequilibrium in early onset disease.	The myeloperoxidase enzyme MPO is expressed specifically in myeloid cells and catalyzes the formation of hypochlorous acid and other cytotoxic oxidants.	9307233	Details
TREM2	MS	ELISA	CSF	up-regulation	Disease risk	Increased CSF levels of sTREM-2, a new marker of microglial activation, in MS and nor-malization upon treatment with either natalizumab or mitoxantrone support a role for microglial activa-tion in active MS.	Microglia-mediated proteolysis of the triggering receptor expressed on myeloid cells-2 (TREM-2) produces soluble TREM-2 (sTREM-2) that can be measured in cerebrospinal fluid (CSF) samples.	26754805	Details
TNFRSF11B	MS	ELISA	PBL and CSF	down-regulation	Disease risk	Our study revealed that changes of RANKL/RANK/OPG axis are associated with MS, particularly the decreased OPG level in the CSF at disease onset. Therefore, these factors may serve as disease bio-markers and molecular targets of novel therapeutic ap-proaches.	Our study focused on the RANKL (receptor acti-vator of nuclear factor-κB ligand)/RANK/OPG (osteoprote-gerin) axis and selected proinflammatory/immunoregula-tory upstream mediators in the peripheral blood (PBL) and cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients	29920500	Details
LEP	MS	ELISA	peripheral blood	up-regulation	Disease risk	Our study implicates a significant role of LEP and LEPR polymorphisms and also leptin levels in the risk of MS and its severity.	Leptin, the product of the ob gene, can modulate the immune responses and also seems to regulate Th1/Th2 balance by promoting a shift from the Th2 to the Th1 inflammatory cytokine pathway.	27105071	Details
LEPR	MS	ELISA	peripheral blood	up-regulation	Disease risk	Our study implicates a significant role of LEP and LEPR polymorphisms and also leptin levels in the risk of MS and its severity.	Leptin, the product of the ob gene, can modulate the immune responses and also seems to regulate Th1/Th2 balance by promoting a shift from the Th2 to the Th1 inflammatory cytokine pathway.	27105071	Details
IFNAR2	MS	ELISA	peripheral blood	up-regulation	Treatment risk	IFN-b administration induces the production of sIFNAR2 in RRMS and higher levels might be associated to the reduction of therapeutic response. Thus, levels of sIFNAR2 could be monitored to optimize an effective response to IFN-b therapy.	Interferon beta receptor 2 subunit (IFNAR2) can be produced as a transmembrane protein, but also as a soluble form (sIFNAR2) generated by alternative splicing or proteolytic cleavage, which has both agonist and antagonist activities for IFN-b.	34975865	Details
IL17A	MS	ELISA	CSF	down-regulation	Disease risk	IL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS.	Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers.	34950135	Details
EDIL3	MS	ELISA	CSF	up-regulation	Disease risk	IL17A, IL2, CD44, and IGF1 may be key extracellular proteins in the pathogenesis of MS. IL17A, Del-1, and resolvinD1 may co-regulate the development of MS and Del-1 is a potential biomarker of MS.	Extracellular proteins are most glycosylated and likely to enter into the body fluid to serve as potential biomarkers.	34950135	Details
MIR29B1	MS	ELISA	peripheral blood	down-regulation	Treatment risk	Our results might provide fundamentals for the development of new markers of the biological effects of IFN-β therapy	Myelin-reactive IFN-γ-producing Th1 cells has been shown to play an important role in the development of MS. MicroRNAs (miRNAs) are a new class of small non-coding RNA molecules about 22 nucleotides long which regulate gene expression post-tran-scriptionally by binding to 3′ UTR of their mRNA targets, and resulting in degradation or transcriptional re-pression of the targeted mRNA.	31421628	Details
IL17A	MS	Immunohistochemistry	meninges	up-regulation	Phenotypic risk	Thus, there is selective migration or survival of RORct-positive cells in MS patient meninges and an association of these cells with ELS.	Because cells expressing the transcriptional regulator reti-noic acid receptor-related orphan receptor-ct (RORct) and producing interleukin 17 (IL17), e.g. T helper 17 cells and lymphoid tissue in-ducer (LTi) cells, have been implicated in the formation of ELS, we studied RORct and IL17 expression in brain tissue from patients with SPMS an assessed their relationships to immune infiltrates and meningeal ELS.	27413074	Details
RORC	MS	Immunohistochemistry	meninges	up-regulation	Phenotypic risk	Thus, there is selective migration or survival of RORct-positive cells in MS patient meninges and an association of these cells with ELS.	Because cells expressing the transcriptional regulator reti-noic acid receptor-related orphan receptor-ct (RORct) and producing interleukin 17 (IL17), e.g. T helper 17 cells and lymphoid tissue in-ducer (LTi) cells, have been implicated in the formation of ELS, we studied RORct and IL17 expression in brain tissue from patients with SPMS an assessed their relationships to immune infiltrates and meningeal ELS.	27413074	Details
NEFL	MS	ELISA	CSF	up-regulation	Phenotypic risk	sNfL levels during the first demyelinating event of MS are associated with greater impair-ment of BBB integrity, immune cell extravasation, and brain lesion activity on MRI.	To investigate the associations of neurofilament light chain (NfL) levels with measures of BBB integrity and central nervous system (CNS) inflammation in MS during the first demyelinating event.	32255388	Details
IL12RB2	MS	ELISA	peripheral blood	up-regulation	Treatment risk	Higher IL-12Rβ2 m R N A l e v e l s were associated with lower risk of relapse. Despite recent reports regarding role of GM-CSF in MS, our study failed to demonstrate its significance as therapy response biomarker, both on the mRNA and protein level.	Cytokines produced by helper T (Th)1 cells, Th17 and regulatory T cells (Treg) are involved in multiple sclerosis (MS) immunopathogenesis.	26439963	Details
Lrrc4	EAE	Immunohistochemistry/Western blot	peripheral blood /spinal cords	down-regulation	Disease risk	We report that LRRC4 is mainly expressed in neuron of spinal cords, and is decreased in the spinal cords of the EAE mice.	Leucine rich repeat containing 4 (LRRC4), also known as netrin-G ligand-2 (NGL-2), belongs to the superfamily of LRR proteins and serves as a receptor for netrin-G2. LRRC4 regulates the formation of excitatory synapses and promotes axon differentiation. Mutations in LRRC4 occur in Autism Spectrum Disorder (ASD) and intel-lectual disability.	33932995	Details
Mbp	rEAE	Immunohistochemistry	lymph nodes	up-regulation	Disease risk	In all four models, expression of golli-MBP BG21 mRNA was increased two- to fivefold in lymph nodes of mice 45 to 60 days post-transfer. Immunohistochemical analysis indicated that expression occurred principally in macrophages within lymph nodes	This larger gene encodes both the ”classic” MBPs as well as the structurally related golli-MBPs. In this study, golli-MBP expression in lymph nodes was examined in four different models of relapsing experimental autoimmune encephalomyelitis (rEAE).	9379062	Details
Creb1	EAE	Immunohistochemistry/Western blot	spinal cords	down-regulation	Phenotypic risk	Based on these results, we suggest that the increased phosphorylation of CREB in EAE lesions was mainly attributable to the infiltration of inflammatory cells and astrogliosis, possibly activating gene transcription,and that its increase in the sensory neurons in the dorsal horns is involved in the generation of neuropathic pain in the rat EAE model.	To investigate whether the phosphorylation of cyclic AMP response element-binding p r o t e i n ( C R E B ) i s i m p l i c a t e d i n t h e p a t hogenesis of experimental autoimmune encephalomyelitis (EAE), the change in the level of CREB phosphorylation was analyzed in the spinal cord of Lewis rats with EAE.	17617386	Details
Cp	EAE	Immunohistochemistry/Western blot	spinal cords	up-regulation	Phenotypic risk	. Based on these observations, we propose that an increase in Cp expression could contribute to tissue damage in early EAE. In addition, endogenous CP either directly or indirectly inhibits astrocyte reactivity during early disease, which could also worsen early disease evolution.	Unexpectedly, ceruloplasmin (Cp), a ferroxidase that converts toxic ferrous iron to its nontoxic ferric form and also promotes the efflux of iron from astrocytes in the CNS, was shown to be highly upregulated (13.2-fold increase) in EAE spinal cord.	24615902	Details
TALDO1	MS	Immunohistochemistry/Western blot	peripheral blood	up-regulation	Treatment risk	The results suggest that TAL may be a more potent immunogen than MBP in MS.	Antibody and T cell–mediated immune responses to oligo-dendroglial autoantigens transaldolase (TAL) and myelin basic protein (MBP) were examined in patients with multi-ple sclerosis (MS).	9077532	Details
Mt1	EAE	Immunohistochemistry	brain/liver	up-regulation	Disease risk	Our data show that AO and DA rats differ in consti-tutive and inductive MT-I gene expression in the brain and in the liver, as well as in the hepatic cytokine profile, suggest-ing that these mechanisms may contribute to the discrep-ancy in the susceptibility to EAE	Compared to the Dark Agouti (DA), the Albino Oxford (AO) rat strain exhibits lower susceptibility to the in-duction of experimental autoimmune encephalomyelitis (EAE). Here, we investigated the potential contribution of the heavy metal-binding proteins metallothioneins (MTs) I/II to these effects	23485922	Details
Kcna3	EAE	immunofluorescence/Western blot	brain	up-regulation	Treatment risk	Our results support the hypothesis that Kv1.3 may be a therapeutic target of interest for MS and add astrocytes to the list of cells whose activation would be suppressed by inhibiting Kv1.3 in inflammatory conditions.	Kv1.3 is a voltage gated potassium channel that has been implicated in pathophysiology of multiple sclerosis (MS).	29574670	Details
ATG16L2	MS	immunoblotting /bead fractionation/matrix-assisted laser desorption/ionizationtime-of-flight (MALDI-TOF) mass spectrometry analyses	peripheral blood	down-regulation	Disease risk	Eleven peptides were significantly different between the two groups with one being identified as a fragment of Atg16L2.	The prolonged survival of autoreactive T cells acts as a primary event to trigger an inflammatory cascade that mediates myelin loss and clinical relapse in MS.	24406150	Details
GAS6	MS	ELISA	CSF	up-regulation	Phenotypic risk	CSF concentration of Gas6 is inversely correlated with the severity of relapse in RR-MS patients but does not predict the subsequent course of the disease.	Growth arrest specific gene 6 (Gas6) protein enhances survival of oligodendrocytes and neurons, and it is involved in autoimmunity.	23781120	Details
Serpinb2	EAE	immunofluorescence/Western blot/ELISA	brain/spinal cords	up-regulation	Disease risk	Upon immunization with OVA in complete Freund's adjuvant, about half of the transgenic mice developed neurological symptoms characteristic of experimental autoimmune encephalomyelitis (EAE).	We have used the 50 flanking sequence of the myelin basic protein gene known to include the core promoter and a strong oligodendrocyte (ODC)-specific enhancer to target expression of the well-studied model antigen ovalbumin (OVA) to ODC in transgenic mice.	16342234	Details
CHI3L1	MS	ELISA	peripheral blood	up-regulation	Phenotypic risk	Plasma CHI3L1 levels were significantly increased in patients with progressive forms of MS compared with RRMS patients and HC.	Chitinase 3-like 1 (CHI3L1) is upregulated in a wide variety of inflammatory conditions. Recent studies have pointed to a role of CHI3L1 in multiple sclerosis (MS) pathogenesis.	22183936	Details
Yap1	EAE	Immunohistochemistry（免疫组化）	optic nerve	up-regulation	Disease risk	compared with control mice, the expression level of YAP was significantly increased in optic nerve of EAE mice	TGF-β signaling	34373754	Details
Ggt1	EAE	immunohistochemistry and FACS	spinal cord	up-regulation	Disease risk	GGT was not detected in healthy spinal cord, but increased in microglia and infiltrating monocyte/macrophages in EAE lesions	GGT degrades the antioxidant glutathione and its dysregulation interferes with redox homeostasis and oxidative stress responses	32284594	Details
C3	MS	immunofluorescence	post-mortem retinas	N/A	Disease risk	Across these cases, the MS patients expressed higher levels of C3 in the GCL than the non-MS controls.	N/A	34487221	Details
B4galt6	EAE	liquid chromotography and tandem mass spectrometry (LC-MS/MS)	brain	up-regulation	Disease risk	we detected increased LacCer levels in the CNS during the progressive phase of NOD EAE	these data suggest that LacCer produced by B4GALT5/6 exacerbates CNS inflammation.	25216636	Details
B4GALT6	MS	liquid chromotography and tandem mass spectrometry (LC-MS/MS)	brain	up-regulation	Disease risk	We found increased expression of B4GALT5 (2.15±0.28 fold) and B4GALT6 (8.26±2.11 fold) in MS lesions, but not in normal appearing white matter (NAWM) or controls	The increased expression of B4GALT5/6 was linked to increased LacCer levels in MS lesions	25216636	Details
Rgcc	MS	Immunohistochemistry	brain	up-regulation	Phenotypic risk	RGC-32 and ECM components are expressed in MS lesions	TGF-β induces the expression of RGC-32 in astrocytes	30006805	Details
Lhb	EAE	Immunohistochemistry	serum	down-regulation	Disease risk	Consistent with our recent work9, serum LH and testosterone levels dropped dramatically during the onset and peak of EAE, compared with control values, but were partially restored towards the end of the disease.	N/A	33903635	Details
Star	EAE	Immunohistochemistry	serum	down-regulation	Disease risk	Consistent with our recent work9, serum LH and testosterone levels dropped dramatically during the onset and peak of EAE, compared with control values, but were partially restored towards the end of the disease.	N/A	33903635	Details
Cyp11a1	EAE	Immunohistochemistry	serum	down-regulation	Disease risk	Consistent with our recent work9, serum LH and testosterone levels dropped dramatically during the onset and peak of EAE, compared with control values, but were partially restored towards the end of the disease.	N/A	33903635	Details
Ccn2	EAE	Western blotting and immunocytochemistry	Spinal Cord	down-regulation	disease risk	In conclusion, our results clearly show that in the absence of RGC-32, CTGF levels remained lower in cultured astrocytes stimulated with TGF-β and in spinal cord astrocytes at the peak of EAE.	We now show for the first time that RGC-32 acts upstream of CTGF in the TGF-β signaling pathway, and RGC-32-mediated regulation of CTGF expression is involved in ECM production.	33569054	Details
Gfap	N/A	Western blotting and immunocytochemistry	Spinal Cord	up-regulation	disease risk	Moreover, Western blot analysis demonstrated significantly higher levels of GFAP protein in WT astrocytes than in RGC-32 KO astrocytes (Figure 4C), whereas vimentin levels were higher in RGC-32 KO astrocytes (Figure 4D), paralleling the differences seen in vivo in the spinal cords.	We now show for the first time that RGC-32 acts upstream of CTGF in the TGF-β signaling pathway, and RGC-32-mediated regulation of CTGF expression is involved in ECM production.	33569054	Details
Pparg	EAE	double immunostaining for macrophages	Spinal Cord	N/A	disease risk	PPAR-γexpression in acute EAE. Immunohistochemistry for PPAR-γ was performed on frozen sections from spinal cords of EAE-affected mice and naive control mice	Initial studies have shown that the presence of the PPAR-gamma ligand 15-deoxy-Delta(12,14)-PGJ(2) (15d-PGJ2) inhibits the proliferation of Ag-specific T cells from the spleen of myelin basic protein Ac(1-11) TCR-transgenic mice. 15d-PGJ2 suppressed IFN-gamma, IL-10, and IL-4 production by both Con A- and myelin basic protein Ac(1-11) peptide-stimulated lymphocytes as determined by ELISA and ELISPOT assay.	11859145	Details
NINJ2	MS	immunocytochemistry	blood	down-regulation	Disease risk	NINJ2 is Down-Regulated after Pro-Inflammatory Stimulation in Monocytes and in THP-1 Cells.	Overall, our results suggest that ninjurin2 could be involved in the transmigration of immune cells into the CNS in pro-inflammatory conditions. Further experiments are needed to elucidate the exact molecular mechanisms.	36360183	Details
ASIC1	MS	immunocytochemistry	brain	up-regulation	Disease risk	In chronic brain lesions of patients with progressive multiple sclerosis, we demonstrate an increased expression of ASIC1 in axons and an association with injury markers within chronic inactive lesions.	N/A	23365093	Details
SPP1	MS	Enzyme-linked Immunosorbent Assay	blood	up-regulation	Disease risk	In contrast, OPN protein levels in primary progressive and secondary progressive MS patients were similar to healthy control levels. Interestingly, active relapsing-remitting patients had higher OPN protein levels than patients without relapses	These increased levels may contribute to a dysregulation of the Th1/Th2 balance as has been suggested by several studies.	12783433	Details
PDCD1	MS	flow cytometry	blood	down-regulation	Disease risk	In the disease remission state, PD-1CD8 T cells were decreased in the peripheral blood of patients with MS and resolved in patients treated with IFN-β treatment who showed immune regulatory cytokine interleukin (IL)-10 expression.	This study uncovered a favorable role of PD-1CD8 T cells against MS and demonstrated that c-Maf-driven IL-10 is an immune regulatory machinery.	35383094	Details
PTPN6	MS	western immunoblot	blood	down-regulation	Disease risk	As previously described, PBMCs of MS patients contained significantly lower levels of SHP-1 protein compared to normal subjects	N/A	19559654	Details
OTUB1	MS	immunohistochemistry	brain	up-regulation	Disease risk	Activated GFAP astrocytes in white matter MS lesions with inflammatory infiltrates and demyelination show an upregulation of OTUB1 (arrows).	Mechanistically, OTUB1 inhibited IFN-γ-induced Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling by K48 deubiquitination and stabilization of the JAK2 inhibitor suppressor of cytokine signaling 1 (SOCS1).	30944096	Details
Slc8a3	EAE	Western blotting and quantitative colocalization	spinal cord	up-regulation	Disease risk	NCX3 Protein Expression is Intensely Upregulatedin the Spinal Cord During the Chronic Stage of EAE	Our findings demonstrate that knocking-out NCX3 impairs oligodendrocyte response and worsens clinical symptoms in EAE without altering the immune T-cell population.	27120265	Details
Bdkrb1	EAE	Western blot	spinal cord	up-regulation	Disease risk	B1R is over-expressed in the spinal cord of EAE mice	The above data constitute convincing experimental evidence indicating that both kinin receptors, especially the B1 subtype, exert a critical role in the establishment of persistent hypersensitivity observed in the EAE model, an action that seems to involve a central inflammatory process, possibly acting on astrocytes.	23454198	Details
Tlr8	EAE	Western blot	spinal cord	up-regulation	Disease risk	Consistent with real-time PCR analysis of the TLR8 mRNA, we found that the abundance of the spinal cord cells expressing TLR8 protein was significantly increased in the EAE spinal cord and this increase was attenuated by 1,25(OH)2D3 treatment, as determined by immunostaining of the spinal cord sections with TLR8 antibody	1,25(OH)2D3 treatment not only significantly reduced TLR8 expression but also the expression or activity of MyD88, IRF-4, IRF-7 and NF-kB in monocytes challenged with TLR8 ligands. TLR8 promoter-luciferase reporter assays indicated that 1,25(OH)2D3 decreases TLR8 mRNA level in part via inhibiting TLR8 gene transcription activity.	23516559	Details
DDX39B	MS	Western blot	blood	down-regulation	Disease risk	Indeed, we showed that a genetic variant in the 5' UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk.	Lastly, our studies uncovered a protective role for DDX39B in the pathogenesis of MS, wherein decreased DDX39B expression results in up-regulation of sIL7R via skipping of IL7R exon 6.	28340352	Details
Ccl6	EAE	Western blot	brain	up-regulation	Disease risk	Significantly elevated levels of CCL2, IL-6, and CXCL10 protein were observed in the brain of LysMCre-SOCS3fl/fl mice compared with SOCS3fl/fl mice	Thus, the absence of SOCS3 in myeloid cells causes enhanced STAT3 and STAT4 activation and elevated cytokine/chemokine expression in the brain.	22411837	Details
Il10	EAE	Western blot	brain	up-regulation	Disease risk	Significantly elevated levels of CCL2, IL-6, and CXCL10 protein were observed in the brain of LysMCre-SOCS3fl/fl mice compared with SOCS3fl/fl mice	Thus, the absence of SOCS3 in myeloid cells causes enhanced STAT3 and STAT4 activation and elevated cytokine/chemokine expression in the brain.	22411837	Details
Cxcl3	EAE	Western blot	brain	up-regulation	Disease risk	Significantly elevated levels of CCL2, IL-6, and CXCL10 protein were observed in the brain of LysMCre-SOCS3fl/fl mice compared with SOCS3fl/fl mice	Thus, the absence of SOCS3 in myeloid cells causes enhanced STAT3 and STAT4 activation and elevated cytokine/chemokine expression in the brain.	22411837	Details
CTLA4	MS	Cytofluorometry study	blood	up-regulation	Disease risk	We analyzed our previous data on CTLA-4 protein expression in CD4 T cells freshly obtained from patients with MS in the context of the CTLA-4 gene polymorphisms determined.	We clearly show, for the first time, that 3′-UTR polymorphisms of the CTLA-4 gene influence both membrane and cytoplasmic CTLA-4 levels, as measured by MFI, and in this way they have impact on disease susceptibility.	19740340	Details
PPARG	MS	Western blot	blood	down-regulation	Disease risk	Surprisingly, MS patients exhibited decreased PPAR-gamma levels compared with controls.	Differences in PPAR-gamma expression were accompanied by changes in PPAR-gamma DNA-binding activity, as preincubation with pioglitazone increased DNA binding of PPAR-gamma.	16210596	Details
IGFBP7	MS	ELISA	blood,cerebrospinal fluid	up-regulation	Disease risk	Compared to NINCs, the level of CSF IGFBP7 was significantly upregulated, and the level of CSF SST was significantly downregulated in the MS group.	N/A	34489947	Details
SST	MS	ELISA	blood,cerebrospinal fluid	down-regulation	Disease risk	Compared to NINCs, the level of CSF IGFBP7 was significantly upregulated, and the level of CSF SST was significantly downregulated in the MS group.	N/A	34489947	Details
Klrb1c	MS	Flow cytometric analysis	blood	up-regulation	Disease risk	Flow cytometric analysis on peripheral blood of healthy donors and patients with multiple sclerosis and rheumatoid arthritis confirmed an upregulation of CD161 at the protein level, showing also a significant excess of CD161(high)CD8(+) T cells in multiple sclerosis.	In summary, our work shows that CD161 expression on CD8 + T cells marks a subset of non-cytotoxic, proinflammatory, CCR6 + T lymphocytes that may play a role in multiple sclerosis immunopathogenesis by acting as effectors and targeting the CNS.	21216829	Details
Ackr3	EAE	Immunostaining and Western Blot	spinal cords	N/A	Disease risk	Of note, in the diseased demyelinating central nervous system, CXCR7 expression is maintained on oligodendroglial cells, whereas CXCR4 could not be detected.	Our findings suggest that a specific activation of the CXCR7 receptor could provide a means to promote oligodendroglial differentiation in the diseased or injured central nervous system.	21154415	Details
NR4A1	MS	Western Blot	blood	down-regulation	Disease risk	We further confirmed the findings by demonstrating low levels of NR4A1 protein in MS2b subjects, RRMS patients, and EAE rats.	We conclude that the altered NR gene network apoptotic machinery prevents the extinction of activated T-cells and promotes the pathogenic process that will lead to the development of clinical disease.	20079437	Details
Nr4a1	EAE	Western Blot	spleen cells	down-regulation	Disease risk	We further confirmed the findings by demonstrating low levels of NR4A1 protein in MS2b subjects, RRMS patients, and EAE rats.	We conclude that the altered NR gene network apoptotic machinery prevents the extinction of activated T-cells and promotes the pathogenic process that will lead to the development of clinical disease.	20079437	Details
Sirt1	EAE	immunofluorescence micrographs	retina	N/A	disease risk	AAV7m8-Mediated Expression of SIRT1 in RGCs Reduces Demyelination but Not Inflammation in the EAE Mouse Model	We conclude that despite minimally affecting the inflammatory response in the optic nerve, AAV7m8-mediated SIRT1 transfer into RGCs has a neuroprotective potential against RGC loss, axon demyelination and vison deficits associated with EAE.	35740955	Details
ACKR1	MS	Immunohistochemistry	brain	up-regulation	disease risk	We confirmed the elevated expression of ACKR1 (coding for the protein DARC, Figure 5, B and C) and LCN2 (coding for the protein lipocalin 2, Figure 5, B and D) on blood vessels in active MS lesions, compared with normal appearing white matter (NAWM) and with control brains.	Venous ECs not only control immune cell trafficking through the expression of CAMs but can also act as immune stimulators or inhibitors through the expression of cell-specific cytokines/chemokines and receptors.	36446612	Details
LCN2	MS	Immunohistochemistry	brain	up-regulation	disease risk	We confirmed the elevated expression of ACKR1 (coding for the protein DARC, Figure 5, B and C) and LCN2 (coding for the protein lipocalin 2, Figure 5, B and D) on blood vessels in active MS lesions, compared with normal appearing white matter (NAWM) and with control brains.	Venous ECs not only control immune cell trafficking through the expression of CAMs but can also act as immune stimulators or inhibitors through the expression of cell-specific cytokines/chemokines and receptors.	36446612	Details
Prmt5	EAE	flow cytometry and immunoblotting	brain	N/A	disease risk	In the SJL mouse relapsing-remitting model of MS, the highest PRMT5 expression in central nervous system-infiltrating cells corresponded to peak and relapse timepoints.	These data indicate that PRMT5 promotes G1/S cell cycle progression and suggest that this effect influences disease severity and/or progression in the animal model of MS.	34168658	Details
NDI1	EAE	Immunofluorescence,Western Blotting	retina	up-regulation	disease risk	In conclusion, targeting the dysfunctional complex I using NDI1 gene can be an approach to address axonal and neuronal loss responsible for permanent disability in MS that is unaltered by current disease modifying drugs.	The 45% optic nerve axonal and 33% retinal ganglion cell (RGC) loss contributed to the permanent loss of visual function in EAE mice were ameliorated by NDI1-mediated prevention of mitochondrial cristae dissolution and improved mitochondrial homeostasis.	31900864	Details
Sort1	EAE	Western Blotting	brain	N/A	disease risk	Accordingly, sortilin was highly expressed by infiltrated perivascular myeloid cells, mainly in vessel cuffs, in the CNS of patients suffering from multiple sclerosis, the most common inflammatory autoimmune disease of the CNS. Yet, sortilin gene-targeted mice (Sort1(-/-)) and chimeras deficient in sortilin in the immune system were as susceptible as wild-type littermates to T cell-dependent experimental autoimmune encephalomyelitis.	Considering our results and recent data from other investigators, we conclude that the proneurotrophin receptor sortilin plays a role in innate, rather than in adaptive, immune processes and, thus, not in autoimmune neuroinflammation.	26566674	Details
Bax	EAE	Western Blot	Spinal cords	N/A	disease risk	In conclusion, ablation of the bax gene attenuates the severity of MOG-induced EAE and emphasizes the importance of apoptosis in the pathogenesis of EAE and MS.	In conclusion, ablation of the bax gene attenuates the severity of MOG-induced EAE and emphasizes the importance of apoptosis in the pathogenesis of EAE and MS.	15050683	Details
Ntf3	MS	Western blots	brain	up-regulation	Disease risk	Transfection converts precursor cells into actively dividing cells that can incorporate 3 H-thymidine into DNA. In the absence of growth factors, a parallel increase in the survival of the transfected cultures was also demonstrated by the MTT test. The final demonstration of biological changes in transfected versus untreated cells was a 10-fold increase in myelin basic protein production observed in Western blots and the direct observation by phase-contrast and electron microscopy of myelin membranes in cocultures with hippocampal neurons. We discuss the future use of this transfected cells in regeneration and functional recovery in experimental models of multiple sclerosis	Oligodendrocyte precursor cells require exogenous neurotrophin-3 (NT-3) for differentiation into oligodendrocytes	15139015	Details
Nfatc1	MS	Western blots	Peripheral blood	up-regulation	Disease risk	NFATc1/ B cells suppress the synthesis of interferon- by T cells in vitro, and these mice exhibit a mild clinical course of experimental autoimmune encephalomyelitis. In large part, the defective functions of NFATc1/ B cells are caused by decreased BCR-induced Ca2+ flux and calcineurin (Cn) activation. By affecting CD22, Rcan1, CnA, and NFATc1/A expression, NFATc1 controls the Ca2+-dependent Cn–NFAT signaling network and, thereby, the fate of splenic B cells upon BCR stimulation	NFATc1 ablation impaired Ig class switch to IgG3 induced by T cell–independent type II antigens, as well as IgG3+ plasmablast formation. Mice bearing NFATc1/ B cells harbor twofold more interleukin 10–producing B cells.	21464221	Details
Mbp	MS	Northern Blotting	spinal cord	up-regulation	Disease risk	The 2-50 mice represent a unique model which will be ideal for investigating the molecular basis of myelin assembly and for developing gene therapy to promote remyelination in conditions such as MS.	These mice carry a transgene comprising 1.3 Kb of the mouse myelin basic protein (BMP) promoter conjugated to a fragment containing exons 2 and 3 of the human c-myc gene	7534359	Details
TALDO1	MS	Western Blot Analysis	Peripheral blood	up-regulation	Disease risk	Presence of crossreactive antigenic epitopes between recombinant TAL-H and HTLV-I/human immunodeficiency virus type 1 (HIV-1) gag proteins was demonstrated by Western blot analysis. The results suggest that molecular mimicry between viral core proteins and TAL-H may play a role in breaking immunological tolerance and leading to a selective destruction of oligodendrocytes in MS	TAL-H is a key enzyme of the nonoxidative pentose phosphate pathway (PPP) providing ribose-5-phosphate for nucleic acid synthesis and NADPH for lipid biosynthesis	7964452	Details
Mog	MS	Southern blotting	Peripheral blood	up-regulation	Disease risk	the T cell reactivity against the immunodominant encephalitogenic region of MOG is characterized by a diverse Vp gene usage and a requirement for the same core epitope. This pattern of reactivity may favor epitope-directed, rather than TCR-targeted, approaches to immunospecific therapy for MOG-related autoimmune disease	Encephalitogenic T cell lines from V(3” mice were also diverse in their TCR Vp gene usage (Vpl, Vp2, Vp6, Vp14 and Vp16). Such a heterogeneous TCR Vp gene expression by pMOG 35-55/I-Ab-reactive T cells from both Vpa and Vpb H-2b mice suggested multiple epitopes within pMOG 35-55. Analysis of the pattern of reactivity by pMOG 35-55-reactive T cells to a set of truncated peptides was not commensurate with independent nested epitopes, but revealed a requirement for recognition of a core sequence, YRSPFSRVV (pMOG 40-48)	8898962	Details
Mog	MS	ELISA	Peripheral blood	up-regulation	Disease risk	Although A strain mice have been reported to have an insertion in BAFF-R, the receptor for BAFF (B cell activation factor from the tumor necrosis factor family), which could explain our results, A.SW mice have no mutations in BAFF-R	MOG but also other antigens, such as gangliosides, histone, blood, liver and kidney proteins	16469392	Details
Lrp1	EAE	Immunofluorescence	Peripheral blood	up-regulation	Disease risk	In experimental autoimmune encephalomyelitis in mice, LRP1 protein expression was substantially increased in the cerebellum and spinal cord. LRP1 colocalized with multiple CNS cell types	These studies establish LRP1 as a major receptor for phagocytosis of degraded myelin, which may function alone or in concert with co-receptors previously implicated in myelin phagocytosis	19299462	Details
Arid5a	EAE	ELISA	Peritoneal macrophages	up-regulation	Disease risk	These results indicate that Arid5a plays an important role in promotion of inflammatory processes and autoimmune diseases.	Arid5a was enhanced in macrophages in response to LPS, IL-1β, and IL-6. Arid5a deficiency inhibited elevation of IL-6 serum level in LPStreated mice and suppressed IL-6 levels and the development of TH17 cells in experimental autoimmune encephalomyelitis. Importantly, Arid5a inhibited the destabilizing effect of Regnase-1 on IL-6 mRNA	23676272	Details
Tcf7l2	MS	Immunohistochemistry	Brains、spinal cords	up-regulation	Disease risk	our data demonstrate that the expression of TCF7L2 in oligodendrocytes is limited to a certain differentiation stage; however the expression of TCF7L2 is neither restricted to the oligodendroglial lineage nor to (re-)myelinating conditions	TCF7L2 binds to coeffectors such as β-catenin or histone deacetylases and thereby activates or inhibits the transcription of downstream genes involved in oligodendroglial differentiation	23977356	Details
TCF7L2	MS	Immunohistochemistry	Brains、spinal cords	up-regulation	Disease risk	our data demonstrate that the expression of TCF7L2 in oligodendrocytes is limited to a certain differentiation stage; however the expression of TCF7L2 is neither restricted to the oligodendroglial lineage nor to (re-)myelinating conditions	TCF7L2 binds to coeffectors such as β-catenin or histone deacetylases and thereby activates or inhibits the transcription of downstream genes involved in oligodendroglial differentiation	23977356	Details
IFNAR1	MS	ELISA	CSF	up-regulation	Disease risk	In vivo recombinant IFN-b–1a treatment induced IFNAR1 and its downstream signaling molecules’ gene expression, suggesting that treatment reconstitutes a deficient endogenous IFN-b regulation of the CD4+ T cells’ pathogenic cytokine production in patients with MS.	We identified that the endogenous IFN-b from serum of RRMS patients induced a significantly lower IFN-inducible gene expression in comparison with healthy controls. In addition, in vitro studies have revealed deficient endogenous and exogenous IFN-b signaling in the CD4+ cells derived from patients with MS. Interestingly, upon inhibition of the endogenous IFN-b signaling by silencing IFN regulatory factor (IRF) 7 gene expression, the resting CD4+ T cells secreted significantly higher level of IL-17A, IL-17F, IL-21, IL-22, and IL-9, suggesting that endogenous IFN-b suppresses the secretion of these pathogenic cytokines.	24850724	Details
TNFSF10	MS	ELISA	venous blood	up-regulation	Disease risk	No significant correlation was detected between the serum TRAIL level and the TRAIL mRNA expression ratio in either group. No statistically significant correlation was found between serum TRAIL levels or the TRAIL mRNA expression ratio with the number of black holes or the bicaudate ratio on MRI. Apoptosis of T lymphocytes is decreased in MS patients, which could be useful when designing treatments. There was no difference in the TRAIL mRNA gene expression ratio between MS patients and controls	The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) molecule is among the potential biomarkers in MS	24913933	Details
Plp1	MS	immunofluorescence	peripheral blood	up-regulation	Disease risk	Treatment of immune-incompetent PLP mutants did not provide evidence for a direct, neuroprotective effect of the medication. When treatment was terminated, no rebound of neuroinflammation occurred and histopathological improvement was preserved for at least 75 days without treatment. After disease onset, teriflunomide halted ongoing axonal perturbation and enabled a recovery of dendritic arborization by surviving ganglion cells. However, neither neuron loss nor clinical features were ameliorated, likely due to already advanced neurodegeneration before treatment onset.	Preventive treatment with teriflunomide attenuated the increase in number of CD8+ cytotoxic effector T cells and fostered the proliferation of CD8+ CD122+ PD-1+ regulatory T cells in the CNS	29970109	Details
TBX21	MS	ELISA	peripheral blood	up-regulation	Disease risk	IFN-γ level at a concentration of 100 μM in comparison with DMSO. Our findings here clearly show that silymarin is an effective regulator for Th1 response in vitro condition. It not only suppresses Th1 proliferating activity but also inhibits T-bet gene expression and IFN-γ production by these cells	T-bet gene expression was significantly decreased in Th1 cells isolated from newly diagnosed and IFN-β-treated RRMS patients after treatment with silymarin compared to DMSO control.	30178232	Details
Prss57	MS	Western blot analysis	peripheral blood	up-regulation	Disease risk	miR‐134‐3p overexpression or PRSS57 silencing enhanced mitochondrial activity of neurons, mitochondrial membrane potential content, CD34+ cell proliferation, while decreasing Cyt C content, inflammatory response, and cell apoptosis. Collectively, overexpression of miR‐134‐3p promotes CD34+ cell proliferation via inhibition of PRSS57 in MS, which may serve as a promising target for MS intervention.	analysis of the targeting relations of miR‐134‐3p and PRSS57 was conducted using online software and dual‐ luciferase reporter gene assay. Furthermore, neuronal functions, inflammatory response, proliferation, and apoptosis of CD34+ cells were assayed by flow cytometry, enzyme‐linked immunosorbent assay, and methyl thiazolyl tetrazolium. IL‐17 and PRSS57 expression increased while miR‐134‐3p expression decreased in the spinal cord from MS rats. miR‐134‐3p could target PRSS57	32619071	Details
Mbp	MS	Western blot	peripheral blood	up-regulation	Disease risk	performing aerobic exercise with CPZ consumption increased MBP gene expression and increased MAG and PLP protein expression, as well as increased myelination of nerve cells in the hippocampus compared to the CPZ group (p < 0.05). It seems that regular aerobic exercise in the MS model controls the destruction of myelin in the nerve cells of hippocampus by upregulating MBP, MAG and PLP, which can have positive effects on cognitive and motor performance	Activation of T lymphocytes elicits an immune response against myelinforming cells, the oligodendrocytes. Oligodendrocytes, myelin sheath and white matter are the main targets of T lymphocytes that penetrate through the central nervous system. It has been stated that in CNS and PNS, MS causes the destruction of the myelin sheath around the axon in the brain and spinal cord, and impairs the ability of nerve cells in the brain and spinal cord to communicate with each other	36341924	Details
Mog	MS	Western blot	peripheral blood	up-regulation	Disease risk	performing aerobic exercise with CPZ consumption increased MBP gene expression and increased MAG and PLP protein expression, as well as increased myelination of nerve cells in the hippocampus compared to the CPZ group (p < 0.05). It seems that regular aerobic exercise in the MS model controls the destruction of myelin in the nerve cells of hippocampus by upregulating MBP, MAG and PLP, which can have positive effects on cognitive and motor performance	Activation of T lymphocytes elicits an immune response against myelinforming cells, the oligodendrocytes. Oligodendrocytes, myelin sheath and white matter are the main targets of T lymphocytes that penetrate through the central nervous system. It has been stated that in CNS and PNS, MS causes the destruction of the myelin sheath around the axon in the brain and spinal cord, and impairs the ability of nerve cells in the brain and spinal cord to communicate with each other	36341924	Details
Mag	MS	Western blot	peripheral blood	up-regulation	Disease risk	performing aerobic exercise with CPZ consumption increased MBP gene expression and increased MAG and PLP protein expression, as well as increased myelination of nerve cells in the hippocampus compared to the CPZ group (p < 0.05). It seems that regular aerobic exercise in the MS model controls the destruction of myelin in the nerve cells of hippocampus by upregulating MBP, MAG and PLP, which can have positive effects on cognitive and motor performance	Activation of T lymphocytes elicits an immune response against myelinforming cells, the oligodendrocytes. Oligodendrocytes, myelin sheath and white matter are the main targets of T lymphocytes that penetrate through the central nervous system. It has been stated that in CNS and PNS, MS causes the destruction of the myelin sheath around the axon in the brain and spinal cord, and impairs the ability of nerve cells in the brain and spinal cord to communicate with each other	36341924	Details
CD40	MS	Western blot	peripheral blood	up-regulation	Disease risk	IFN-r treatment leads to the activation of NF-B in a time-dependent manner, which is inhibited in the presence of anti-TNF-β-neutralizing antibody. These results indicate that IFN-+-induced TNF-β production and subsequent NF-B activation are integral parts of the mechanism of IFN-+-induced CD40 expression	we have discovered that a major component of IFN-r-induced CD40 expression involves the endogenous production of the cytokine TNF-r. The inclusion of anti-TNF-r-neutralizing antibody significantly inhibits IFN-r-induced CD40 mRNA and CD40 promoter activity. IFN-r-induced CD40 protein expression is attenuated in TNF-r-deficient microglia and can be restored with exogenous TNF-r. Sitedirected mutagenesis studies demonstrate that three of the four NF-B elements in the CD40 promoter are required for IFN-r-induced CD40 promoter activity	11830590	Details
MBP	MS	Western blot	peripheral blood	up-regulation	Disease risk	Our data indicate that this inducible gene expression system is useful for the study of gene function in vivo and for the development of transgenic animal models relevant to human diseases such as multiple sclerosis	Upon the addition of doxycycline (DOX, a tetracycline derivative), tet transactivators became activated and bound to one or more TRE, leading to the activation of the CMV promoter and the expression of GFP in oligodendrocytes. We have successfully expressed GFP and luciferase at high levels in oligodendrocytes in a timeand dose-dependent fashion. In the absence of DOX, there was almost no GFP expression in oligodendroglial cultures. Graded levels of GFP expression were observed after induction with DOX (0.5 to 12.5 jig/ml).	10203578	Details
paddle	MS	Northern blots	brain	up-regulation	Disease risk	From our data we concluded that up-regulation of myelin-associated PAD was responsible for the increase in citrullinated MBP in our transgenic mice prior to onset of clinical or pathological signs of demyelination. We postulate that a similar mechanism may be responsible for the increase in citrullinated MBP in multiple sclerosis	Citrulline in proteins arises as a post-translational modification of arginine. In our original studies we isolated myelin basic protein (MBP) which contained six citrullinyl residues, two near the N terminal portion and four near the C-terminal portion of the molecule (Wood and Moscarello 1989) from normal human brain. This citrullinated MBP accounted for about 20% of the total MBP in normal, adult human brain	12064481	Details
FGF2	MS	Immunocytochemistry	brain	up-regulation	Disease risk	The data presented here demonstrate that upon induction with Dox, CG4-FGF2 cells retain their capacity to differentiate in vitro. Additionally, we provide evidence that FGF2 release by engineered cells enhance proliferation and migration of cells of the oligodendrocyte lineage without preventing them to differentiate and myelinate axons in vitro	we have developed a genetically modified CG4 cell line (CG4-FGF2), which are able to release significant amounts of fibroblast growth factor 2 (FGF2) in a controlable fashion in vitro.	14769383	Details
NOS2	MS	Northern blots	Brain	up-regulation	Disease risk	This study delineates a novel role of dsRNA in inducing the expression of iNOS through dsRNAactivated protein kinase (PKR)-mediated activation of NF-UB and p38-mediated activation of C/EBPL in human astroglia that may participate in virus-induced neurological abnormalities	This study underlines the importance of double-stranded RNA (dsRNA), the active component of a viral infection, in inducing the expression of inducible nitric oxide synthase (iNOS) in human astroglia. DsRNA in the form of synthetic polyinosinic-polycytidylic acid (poly IC) induced expression of iNOS and iNOS promoter-driven luciferase activity through activation of nuclear factor (NF)-UB and CCAAT/enhancer-binding proteinL (C/EBPL)	15063753	Details
Cd40	MS	Immunocytochemistry	Brain	up-regulation	Disease risk	LPS induces acetylation and phosphorylation of histones H3 and H4 and the recruitment of NF-rB, STAT-1, and RNA polymerase II on the CD40 promoter in vivo in a time-dependent manner, all events important for CD40 gene transcription. These results indicate that both LPS-induced NF-βB activation and endogenous production of IFN-r that subsequently induces STAT-1 activation play critical roles in the transcriptional activation of the CD40 gene by LPS.	Blocking IFN-r–induced activation of STAT-1 by IFN-r–neutralizing antibody reduces LPS-induced CD40 gene expression	16020513	Details
Ndufa13	MS	ELISA	spleens	up-regulation	Disease risk	The levels of Th1 and Th17 cells were measured via flow cytometry, immunofluorescence, and immunohistochemical analysis. IL-17A and IFNγ expression levels were assessed via ELISA and quantitative PCR. IL-17A expression decreased and IFNγ expression increased in EAE mice that received injections of the GRIM19 OVN. GRIM19 transgenic mice expressed more IFNγ than did wild-type mice; this inhibited EAE development. However, the effect of GRIM-19 overexpression on the EAE of IFNγ-KO mice did not differ from that of the empty vector. GRIM-19 expression was therapeutic for EAE mice, elevating the IFNγ level. GRIM-19 regulated the Th17/Treg cell balance	The protein encoded by the Gene Associated with Retinoid-Interferon-Induced Mortality-19 (GRIM-19) is located in the mitochondrial inner membrane and is homologous to the NADH dehydrogenase 1-alpha subcomplex subunit 13 of the electron transport chain	33163248	Details
Plp1	MS	ELISA、Western blots	spleens	up-regulation	Disease risk	Widespread anti-PLP mAb recognition of neurons suggests a novel potential pathophysiologic mechanism in MS patients, i.e., that anti-PLP antibodies associated with demyelination might simultaneously recognize pgf epitopes in neurons, thereby affecting their functions	In the present study, PLP knockout and wild-type mice were immunized with PLP and PLP peptides, and a large panel of monoclonal antibodies (mAbs) with reactivities to different PLP regions was generated. Selected mAbs were characterized for their reactivities to 1) whole PLP and PLP peptides by ELISA, 2) PLP and DM-20 on Western blots, and 3) live and fixed oligodendrocytes and normal human CNS tissue by immunohistochemistry. The results demonstrated the epitope specificity of the mAbs and their applicability to immunohistochemical studies of paraffin-embedded tissue samples	16416423	Details
Nfe2l2	MS	Western Blot.	Bone marrow mesenchymal stem cells	up-regulation	Disease risk	We demonstrated that MMF activated Nrf2 and induced anti-oxidant Nrf2 target gene expression in bone marrow-derived mesenchymal stem cells.	The multiple sclerosis drug Tecfidera contains dimethylfumarate, which is rapidly metabolized to monomethylfumarate (MMF); MMF is thought to function through nuclear factor erythroid-derived-2-like-2 (Nrf2), a transcription factor activated by oxidative stress which induces the expression of endogenous antioxidant systems. We hypothesized that MMF-elicited increases in anti-oxidants would inhibit osteopenia induced by ovariectomy, as a model of aging-related osteoporosis and high oxidative stress	31362266	Details
Tnfaip3	MS	Immunological Procedures	corpus callosum and in the spinal cord	up-regulation	Disease risk	The results suggest that TNFAIP3 in myeloid cells critically controls the development of M-MDC in lymphoid organ and of microglia in the CNS.	The intracellular-ubiquitin-ending-enzyme tumor necrosis factor alpha-induced protein 3 (TNFAIP3) is a potent inhibitor of the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway.	32325694	Details
P2rx4	NMOSD	Immunohistochemistry	CSF	up-regulation	Disease risk	Conclusion We showed that AQP4-Ab promotes extracellular ATP release from astrocytes, and ATP-mediated neuropathic pain was suggested in NMOSD rat model. Our results indicate the critical role of ATP in the pathogenesis of AQP4-Ab–mediated pain development	Development of mechanical allodynia was confirmed in rAQP4 IgG–treated rats. AQP4-Ab–mediated extracellular ATP release from astrocytes was observed in vitro, and pharmacological inhibition of ATP receptor reversed mechanical allodynia in the rAQP4 IgG–treated rats	34419102	Details
TF	MS	Immunofluorescence	oligodendrocyte progenitors	up-regulation	Disease risk	analysis of the secretome demonstrated that SPC-OLPs contained 3.5 times more Tf than that of GC cells, indicating that Tf is gravitationally regulated, opening two main fields of study to understand the upregulation of the Tf gene and secretion of the protein that keep OLPs at a progenitor stage rather than moving forward to more mature phenotypes. Alternatively, because Tf is an autocrine and paracrine factor in the central nervous system (CNS), in the absence of neurons, it accumulated in the secretome collected after space flight	the iron carrier glycoprotein Tf, previously described as an early marker for OLPs, was expressed ectopically in the nucleus of all SPC-OLPs. In contrast, their GC counterparts expressed it exclusively in the cytoplasm, as previously described	35743828	Details
Cd80	MS	Immunocytochemical	brain	up-regulation	Disease risk	The above results indicate that local paracrine and autocrine mechanisms may be involved in a downregulatory loop that would inhibit B7 expression within the CNS and therefore reduce the potential for local antigen presentation.	IFNg was a weak inducer of B7-2 mRNA and immunoreactivity in microglia primary cultures obtained from the neonatal mouse brain, whereas lipopolysaccharide, tumour necrosis factor-a, colony-stimulating factors and interleukin-1b did not affect microglial B7-2 expression	9003248	Details
Cd86	MS	Immunocytochemical	brain	up-regulation	Disease risk	The above results indicate that local paracrine and autocrine mechanisms may be involved in a downregulatory loop that would inhibit B7 expression within the CNS and therefore reduce the potential for local antigen presentation.	IFNg was a weak inducer of B7-2 mRNA and immunoreactivity in microglia primary cultures obtained from the neonatal mouse brain, whereas lipopolysaccharide, tumour necrosis factor-a, colony-stimulating factors and interleukin-1b did not affect microglial B7-2 expression	9003248	Details
Ifnb1	MS	ELISA	Peripheral blood	up-regulation	Disease risk	These results indicate that IFNb, which is currently used as a treatment for relapsing, remitting multiple sclerosis, is a potent immunomodulatory and antiinflammatory cytokine in CIA and should be considered for the treatment of rheumatoid arthritis	supernatants from these engineered fibroblasts inhibited collagen-induced interferon-g secretion from lymph node cells, and reduced the levels of tumor necrosis factor a and interleukin-12 produced by lipopolysaccharide/IFNg-treated bone marrow–derived macrophages. This effect was specific, since it was reversed with anti-IFNb polyclonal antibodies	9920019	Details
Tnf	ischemic or traumatic brain injury	electrophoretic mobility shift assays (EMSA)	brain	up-regulation	Disease risk	Endotoxin treatment increased NF-6B expression (P < 0.05) both in vivo and vitro compared with control (untreated) cells. Ketamine suppressed endotoxin-induced neuronal NF-6B activation in a dose-dependent manner (P < 0.05, except for the 10–5M concentration in vitro) both in vivo and vitro	whether ischemic or traumatic, results in an increase in brain cell neuronal NF-6B expression, which causes increased tissue concentrations of the proinflammatory cytokines, including IL-1 and TNF-a resulting in neuronal inflammation, injury, and cell death	11032280	Details
cysC	MS	Immunoassay design	serum and CSF	up-regulation	Disease risk	In CSF, the signal produced by the dimerized CysC was multifold compared to serum samples. Similar levels of total CysC and dimer were detected in both patient groups comprising of MS patients and patients with symptoms of the CNS, but confirmed not to have MS. The dimeric CysC assay could provide a valuable tool to explore CysC dimerization and oligomerization originating from body fluids or as conducted as a part of folding studies.	The amyloid formation by a L68Q variant CysC accounts for the hereditary CysC amyloid angiopathy (HCCAA)	20202469	Details
NFATC2	MS	Western blot	brain	up-regulation	Disease risk	These data demonstrate that TNF-a promotes FasL expression through NFAT activation in neuroblastoma cells and this event leads to increased apoptosis through independent caspase-3 activation.	Gal4hNFATc2(1–415) construct contains the first 415 amino acids of the human NFATc2 fused to the DNA binding domain (DBD) of the yeast Gal4 transcription factor (amino acids 1–147) in the parental Gal4-DBD plasmid	21298033	Details
Hdac1	MS	Western blot	Peripheral blood	up-regulation	Disease risk	Elevated nuclear FTY720-P is associated with decreased HDAC activity and increased histone acetylation at H3K18 and H3K23 in LM/Bc MEFs. Treatment of LM/Bc MEFs with FTY720 and a selective Sphk2 inhibitor, ABC294640, significantly reduces the amount of FTY720-P that accumulates in the nucleus. The data provide insight into the relative amounts of FTY720-P generated in the nuclear versus cytoplasmic subcellular compartments after FTY720 treatment and the specific Sphk isoforms involved	The results of this study suggest that FTY720-induced NTDs may involve multiple mechanisms, including: (1) sustained and/or altered S1P receptor activation and signaling by FTY720-P produced in the cytoplasm and (2) HDAC inhibition and histone hyperacetylation by FTY720-P generated in the nucleus that could lead to epigenetic changes in gene regulation	26719367	Details
BDNF	MS	Western blot	Human U251 glioma cells	up-regulation	Disease risk	These results indicated that phosphorylation of GSK3β at Ser9 might be involved in HERV-W env-induced BDNF expression, and will hopefully improve our understanding of the role of HERV-W env in neurological and psychiatric diseases	GSK3β signaling pathway in U251 cells	27235578	Details
Nfe2l2	MS	immunohistochemistry	brain	up-regulation	Disease risk	Our findings suggest that DMF treatment confers neuroprotection after TBI via preservation of brain GSH levels rather than by modulating neuroinflammation.	DMF-treated mice displayed less neurological deficits than vehicle-treated mice and reduced histopathological brain damage.At the same time, the TBI-evoked depletion of brain GSH was prevented by DMF treatment.However, Nrf2 target gene mRNA expression involved in antioxidant and detoxifying pathways was increased in both treatment groups at 4 dal.	28921587	Details
Nos2	MS	Immunofluorescence Analysis	brain	up-regulation	Disease risk	We therefore conclude that LX007 exhibits anti-inflammatory effects in LPS-stimulated microglial cells by inhibiting pro-inflammatory mediators corresponding to the downregulating of MAPKs and NF-κB activation. Taken together, the present study indicated that LX007 may have potential to be developed into an anti-inflammatory agent in the future.	LX007 inhibited lipopolysaccharide (LPS)-stimulated nitric oxide (NO) and prostaglandin E2 (PGE2) expression, as well as their regulatory geneinducible NO syntheses (iNOS) and cyclooxygenase-2 (COX-2) in LPS-treated primary microglia. LPS-induced production from microglia of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF-α) was also significantly attenuated by LX007. Mechanistically, LX007 potently suppressed phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) p65 nuclear translocation in LPS-induced microglia.	29198015	Details
TREM1	MS	Western blotting	brain、CSF and plasma tests	down-regulation	Disease risk	sTREM2 in the CSF of cases with Alzheimer’s disease, and multiple sclerosis was not signifcantly altered in our series	compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia	33881612	Details
Cxcl10	acute encephalomyelitis and chronic demyelinating disease	Immunohistochemistry	brain 、spinal cords	down-regulation	Disease risk	notably CRG-2, in the initiation and maintenance of an inflammatory response following infection with MHV, which is important in contributing to demyelination.	regulation of chemokine expression contributes to the initiation and maintenance of the chronic inflammatory response that is observed in MHV-infected mice. Production of chemokines, notably CRG-2, by resident astrocytes may aid in attracting T cells and microglia/macrophage to areas in which MHV is present, and these cells participate in the demyelination process through, as of yet, undiscovered mechanisms	9551936	Details
Ccl5	acute encephalomyelitis and chronic demyelinating disease	Immunohistochemistry	brain 、spinal cords	down-regulation	Disease risk	notably CRG-2, in the initiation and maintenance of an inflammatory response following infection with MHV, which is important in contributing to demyelination.	regulation of chemokine expression contributes to the initiation and maintenance of the chronic inflammatory response that is observed in MHV-infected mice. Production of chemokines, notably CRG-2, by resident astrocytes may aid in attracting T cells and microglia/macrophage to areas in which MHV is present, and these cells participate in the demyelination process through, as of yet, undiscovered mechanisms	9551936	Details
Mbp	EAE	ELISA	Peripheral blood、CSF	down-regulation	Disease risk	Since the MVV peptide was not recognised by antibodies or T lymphocytes from MVV-infected and encephalic sheep, it was concluded that epitope mimicry of this 2 1.5 kDa MBP peptide by the similar MVV pal peptide was not contributing to the immunopathogensis of Visna. The slight antibody response to MBP and the MBP peptide can be attributed to by-stander effects of the immunopathology of MVV-induced encephalitis.	Weise and Carnegie found a region of sequence similarity between the pal gene of the Maedi Visna virus (MVV), which induces demyelinating encephalitis in sheep, and myelin basic protein (MBP), which is known to induce experimental allergic encephalitis (EAE) in laboratory animals	9014312	Details
S1pr3	MS	Western blotting	brain	up-regulation	Disease risk	S1P3, through its ability to activate RhoA and its upregulation in astrocytes, plays a unique role in inducing inflammatory responses and should be considered as a potentially important therapeutic target for CNS disease progression	S1P induces expression of all of these genes through coupling to the Gα12/13 proteins which activate RhoA	28577576	Details
P2RY12	MS	immunocytofluorescence	Human Embryonic Stem Cell, Oligodendrocyte Progenitor Cell	up-regulation	Disease risk	Elucidation of the expression pattern of purinergic receptors and the effects of different subtypes of these receptors in hESC-OPCs may have a promising role in future cell-based therapy or drug design for demyelinating disease.	A1 AR activation in hESC-derived OPC (hESC-OPCs) developmental processes such as proliferation and differentiation in vitro	28836401	Details
AKT1	chronic neurodegenerative diseases (e.g., Alzheimer′s disease, Parkinson′s disease, multiple sclerosis, amyotrophic lateral sclerosis)	Western blotting	BV2 microglial cell	up-regulation	Disease risk	The anti-inflammatory effects of LXW7 may be associated with the inhibition of microglial activation via Akt/NF-κB and JNK/MAPK signaling pathways by blocking integrin αvβ3 receptor. The present study′s findings suggest that LXW7 has a substantial therapeutic potential for treating inflammatory and neurodegenerative diseases.	Akt/NF-κB and JNK/MAPK signaling pathways by blocking integrin αvβ3 receptor	31732449	Details
S100b	MS	Western blot	brain	up-regulation	Disease risk	our electron microscopy data show that inhibition of the S100B–RAGE axis prevents axonal damage and myelin loss, in parallel with enhanced functional remyelination, as observed by the presence of thinner myelin sheaths when compared with Control. Overall, our data implicate the S100B–RAGE axis in the extent of myelin and neuronal damage, as well as in the inflammatory response that follows	we confirmed that LPC-induced demyelination increased S100B and RAGE expression, while RAGE antagonist FPS-ZM1 markedly reduced their content and altered RAGE cellular localization	33100970	Details
Hmox1	MS	Western blot	bone marrow (BM)	up-regulation	Disease risk	TLR9 induced IL-10 is under the control of HO-1 activity both in vitro and in vivo. Therapeutic enhancement of the HO-1/IL-10 axis in a murine model was able to significantly ameliorate MAS disease activity. These results suggest targeting HO-1 may be viable as a MAS therapeutic target, and DMF and MmF should be considered in investigations of MAS therapy	HO-1 is required for the majority of TLR9 induced IL-10	33191652	Details
FOXP3	MS、primary immune thrombocytopenia	Immunohistochemistry	Peripheral blood	up-regulation	Disease risk	CD4+ Foxp3+ T cells were increased in SLE patients compared with organ-specific autoimmune disease controls or healthy controls. Circulating CD4+ Foxp3+ T cells were correlated with the disease activity of SLE. The increased CD4+ Foxp3+ T cells in active SLE patients were mainly derived from thymus-derived Treg (tTreg) cells, as determined by a demethylated TSDR status, and represented a unique phenotype, upregulated expression of CD49d, CD161, and IL-17A, with immunosuppressive ability comparable to that of healthy controls. Finally, CD4+ Foxp3+ IL-17A+ cells were infiltrated into the renal biopsy specimens of patients with active lupus nephritis.	A unique tTreg subset with dichotomic immunoregulatory and T helper 17 phenotypes is increased in the circulation of SLE patients and may be involved in the pathogenic process of SLE	32317002	Details
Il1	inflammatory response, cell death, and edema development	Immunohistochemical	brain	up-regulation	Disease risk	Intracerebral inflammation, death of intrinsic CNS cells, and vasogenic edema can be mediated by IL-1β, and TNF can cause vasogenic edema. Suppression of these cytokines in the clinical setting may improve outcome	cell death occurred via the apoptotic pathway. The TNF did not induce inflammation or DNA fragmentation within the analyzed time period. Both IL-1 and TNFcaused vasogenic edema, as measured by specific gravity and albumin staining. The edematous effect of TNF persisted 72 hours after injection , whereas the IL-1β–treated animals had normalized by that time.	10616089	Details
CCL5	MS	ELISA	brain	up-regulation	Disease risk	glatiramer acetate may exert its therapeutic effect in MS partially through inhibiting NF-kB activation and chemokine production	our electrophoretic mobility shift assays of nuclear extracts from TNF-a-treated cells reveal an increase in DNA-binding activity specic for the nuclear factor-kappa B (NF-kB) binding site, in the 50 -ˉanking promoter region of the human RANTES gene, and that this increase in NF-kB binding activity is prevented by pretreatment with glatiramer acetate or the NF-kB inhibitors.	11389171	Details
CCL5	MS	ELISA	brain	up-regulation	Disease risk	U-105MG cells treated with TNF-a and IL-l alone or in combination markedly induced increases in the rate of transcription of the RANTES chemokine gene	IFN-y alone had little effect on RANTES production in both U-373MG and U-105MG cells, while TNF-a or IL-I alone had differential effects in the two cell lines. Low levels of RANTES chemokine were detected in culture supernatants from U-373MG cells. By contrast, TNF-a or IL-l dramatically increased RANTES secretion in U-105MG cells. Interestingly, different combination treatments of cells with the three cytokines synergistically induced RANTES release from both U373MG and U-105MG cells.	11408956	Details
Nos2	stroke, multiple sclerosis, Parkinson’s disease, and HIV dementia	immunoblot analysis	brain	up-regulation	Disease risk	we demonstrate that, as expected, iNOS activity in astrocytes is governed by arginine transported into the cell from the extracellular medium. Unexpectedly, however, we found that arginine concentration not only regulates NO production by limiting availability of substrate for iNOS, it also regulates iNOS expression via translational control of iNOS mRNA	inhibition of iNOS activity by arginine depletion in stimulated astrocyte cultures occurs via inhibition of translation of iNOS mRNA. After stimulation by cytokines, uptake of L-arginine negatively regulates the phosphorylation status of the eukaryotic initiation factor (eIF2a), which, in turn, regulates translation of iNOS mRNA. eIF2a phosphorylation correlates with phosphorylation of the mammalian homolog of yeast GCN2 eIF2a kinase. As the kinase activity of GCN2 is activated by phosphorylation, these findings suggest that GCN2 activity represents a proximal step in the iNOS translational regulation by availability of L-arginine. These results provide an explanation for the arginine paradox for iNOS and define a distinct mechanism by which a substrate can regulate the activity of its associated enzyme	12655043	Details
Nos2	MS	Immunoblot analysis	brain	up-regulation	Disease risk	In summary, we show that TNL inhibits LPS-induced activation of iNOS by inhibiting the activation of PKCd and ERK-2, thus possibly affecting post-translational modification of iNOS mRNA. Our result may have further implications for the use of TNL as a novel therapeutic agent in neurological disorders associated with activation of microglia and increased NO release, including multiple sclerosis	PKCd and ERK-2	14505805	Details
Rag1	MS	immunohistochemistry	Peripheral blood	up-regulation	Disease risk	These findings provide strong evidence that a primary glial damage can cause secondary immune reactions of pathological significance as it has been suggested for some forms of multiple sclerosis and other leukodystrophies.	Overexpression of the major myelin protein of the CNS, proteolipid protein (PLP), leads to late-onset degeneration of myelin and pathological changes in axons	16885234	Details
Apoe	MS	Western Blot	aortic valve and sinuses of Valsalva	up-regulation	Disease risk	In marked contrast to the embryonic lethality seen in mice lacking class Ia PI3-kinase, germ-line deletion of p110r results in mice that exhibit normal viability, longevity, and fertility, with relatively well tolerated defects in innate immune and inflammatory responses that may play a role in diseases such as atherosclerosis and multiple sclerosis. Our results not only shed mechanistic light on inflammatory signaling during atherogenesis, but further identify p110r as a possible target for pharmacological intervention in the primary and secondary prevention of human atherosclerotic cardiovascular disease	Inflammatory cell activation by chemokines requires intracellular signaling through phosphoinositide 3-kinase (PI3-kinase) and the PI3-kinase-dependent protein serine/threonine kinase Akt	17483449	Details
da	MS	Immunohistochemical analysis	Peripheral blood	up-regulation	Disease risk	demonstrate that DA RNA or a DA protein(s) is toxic to myelin-synthesizing cells. This Cre/loxP transgenic system allows for spatially and temporally controlled expression of the viral transgene and is valuable for clarifying nonimmune (and immune) mechanisms of demyelination induced by TMEV as well as other viruses	Cre/loxP transgenic system	18400855	Details
IL2	multiple sclerosis, psoriasis and type 1 diabetes	Western blot	Peripheral blood	up-regulation	Disease risk	clofazimine is a promising immunomodulatory drug candidate for treating a variety of autoimmune disorders.	Clofazimine was initially identified as an inhibitor of intracellular T cell receptor-mediated signaling leading to the transcriptional activation of human interleukin-2 gene in T cells from a screen of the Johns Hopkins Drug Library. A systematic mechanistic deconvolution revealed that clofazimine selectively blocked the Kv1.3 channel activity, perturbing the oscillation frequency of the calcium-release activated calcium channel, which in turn led to the inhibition of the calcineurin-NFAT signaling pathway.	19104661	Details
Csf1	myelin disorders.	Immunohistochemistry	brain	down-regulation	Disease risk	A similar decrease was seen at 7 months of age. Morphometric studies of spinal cord myelination showed that development of myelin was not affected in op/op mice. In response to a stab wound, the increase in the number of microglia/macrophages in op/op mice was significantly less pronounced than that in wild-type control. These findings demonstrate that this mutant is a valuable model in which to study roles of microglia/macrophages in the pathophysiology of myelin disorders	The osteopetrotic (op/op) mouse has reduced numbers of cells of monocyte lineage as a result of an inactivating mutation in the colony stimulating factor-1 gene	19396881	Details
OLIG2	multiple sclerosis or traumas such as spinal cord injury	Immunocytochemical characterization	brain	up-regulation	Disease risk	OPCs were differentiated as spheres in defined serum-free medium supplemented with recombinant human growth factors. A broad gene expression analysis revealed that this OPC population expressed Olig1/2, Sox10, PDGFR, Nkx2.2, Nkx6.2, oligodendrocyte-myelin glycoprotein, myelin basic protein (MBP), and proteolipid protein (PLP). According to quantitative RTPCR analyses addition of ciliary neurotrophic factor (CNTF) upregulated the Olig2 mRNA levels in the OPC population. According to the flow cytometry analyses the OPC population was N90% NG2-positive, N80% PDGFR-positive, and N60% CD44-positive, and further matured into O4- (45%) and GalC- (80%) positive oligodendrocyte populations when cultured on top of human extracellular matrix proteins, which were used instead of Matrigel. In addition, OPCs matured into myelin-forming cells when cocultured with neuronal cells.	OPC population expressed Olig1/2, Sox10, PDGFR, Nkx2.2, Nkx6.2	20538536	Details
Il2	neurodegenerative diseases (e.g., Alzheimer’s disease), neurodevelopmental disorder (e.g., autism, schizophrenia), and autoimmune diseases including multiple sclerosis	Immunohistochemistry	brain	up-regulation	Disease risk	Models such as the congenic IL-2 knockout mice bred on immunode fi cient backgrounds coupled with immune reconstitution strategies can be valuable to test novel hypotheses such as our postulation that changes in the brain’s endogenous neuroimmunological milieu that occur with the loss of brain IL-2 gene expression may be involved in initiating CNS autoimmunity. Thus, further research using this approach may help to delineate further the complexity of IL-2 biology in the brain and immune system	It is noteworthy that IL-2 has been shown to be one of the most potent modulators of acetylcholine (ACh) release from rat hippocampal slices	22933152	Details
TLR4	MS	Western blot	brain	up-regulation	Disease risk	We demonstrated that the ENV protein is present in close proximity to TLR4-expressing oligodendroglial precursor cells adjacent to multiple sclerosis lesions. Human and rat oligodendroglial precursor cells expressed TLR4, and the ENV-mediated activation of TLR4 led to the induction of proinflammatory cytokines and inducible nitric oxide synthase as well as the formation of nitrotyrosine groups and a subsequent reduction in myelin protein expression.Interpretation: Our findings suggest that ENV-mediated induction of nitrosative stress via activation of TLR4 results in an overall reduction of the oligodendroglial differentiation capacity, thereby contributing to remyelination failure.Therefore, pharmacological or antibody-mediated inhibition of ENV may prevent the blockade of myelin repair in the diseased or injured central nervous system.	Human and rat oligodendroglial precursor cells expressed TLR4, and the ENV-mediated activation of TLR4 led to the induction of proinflammatory cytokines and inducible nitric oxide synthase as well as the formation of nitrotyrosine groups and a subsequent reduction in myelin protein expression	23836485	Details
Tlr4	MS	Western blot	brain	up-regulation	Disease risk	We demonstrated that the ENV protein is present in close proximity to TLR4-expressing oligodendroglial precursor cells adjacent to multiple sclerosis lesions. Human and rat oligodendroglial precursor cells expressed TLR4, and the ENV-mediated activation of TLR4 led to the induction of proinflammatory cytokines and inducible nitric oxide synthase as well as the formation of nitrotyrosine groups and a subsequent reduction in myelin protein expression.Interpretation: Our findings suggest that ENV-mediated induction of nitrosative stress via activation of TLR4 results in an overall reduction of the oligodendroglial differentiation capacity, thereby contributing to remyelination failure.Therefore, pharmacological or antibody-mediated inhibition of ENV may prevent the blockade of myelin repair in the diseased or injured central nervous system.	Human and rat oligodendroglial precursor cells expressed TLR4, and the ENV-mediated activation of TLR4 led to the induction of proinflammatory cytokines and inducible nitric oxide synthase as well as the formation of nitrotyrosine groups and a subsequent reduction in myelin protein expression	23836485	Details
Nos2	inflammatory effects	Western blot analysis	brain	up-regulation	Disease risk	we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-infl ammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-infl ammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-infl ammatory effects of kalopanaxsaponin A in LPS-stimulated microglia	JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS	24244819	Details
Tnf	inflammatory effects	Western blot analysis	brain	up-regulation	Disease risk	we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-infl ammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-infl ammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-infl ammatory effects of kalopanaxsaponin A in LPS-stimulated microglia	JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS	24244819	Details
Ptgs2	inflammatory effects	Western blot analysis	brain	up-regulation	Disease risk	we showed that kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus, inhibited inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor (TNF)-α expression in lipopolysaccharide (LPS)-stimulated microglia, while kalopanaxsaponin A increased anti-infl ammatory cytokine interleukin (IL)-10 expression. Subsequent mechanistic studies revealed that kalopanaxsaponin A inhibited LPS-induced DNA binding activities of NF-κB and AP-1, and the phosphorylation of JNK without affecting other MAP kinases. Furthermore, kalopanaxsaponin A inhibited the intracellular ROS production with upregulation of anti-infl ammatory hemeoxygenase-1 (HO-1) expression. Based on the previous reports that JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS, our data collectively suggest that inhibition of JNK pathway plays a key role in anti-infl ammatory effects of kalopanaxsaponin A in LPS-stimulated microglia	JNK pathway is largely involved in iNOS and proinfl ammatory cytokine gene expression via modulating NF-κB/AP-1 and ROS	24244819	Details
ERVW-1	neurodegenerative disease	Western blotting	Peripheral blood	up-regulation	Disease risk	AgNPs induce syncytin-1 expression in leukaemic cell lines	FA-AML1 cells were more sensitive overall than MOLT-4 to treatment with the smaller 7nm sized AgNp’s being the most toxic in these cells	27576335	Details
CYP4F2	optic neuritis (ON)	ELISA	Peripheral blood	up-regulation	Disease risk	The higher IL-17A levels were found to be associated with ON, while allele A at rs1558139 was associated only with ON with MS in male patients	In the central nervous system, IL-17A is associated with a wide range of neuropathological disorders (MS, epilepsy episodes of ischemic brain disorders). IL-17A, acting on spinal nerve roots and the spinal cord, contributes to neuropathic and inflammatory pain promotion through pain receptors.Also, IL-17A is very important to damaged sympathetic axons which innervate the cornea regeneration and growth.	29736281	Details
IL17A	optic neuritis (ON)	ELISA	Peripheral blood	up-regulation	Disease risk	The higher IL-17A levels were found to be associated with ON, while allele A at rs1558139 was associated only with ON with MS in male patients	In the central nervous system, IL-17A is associated with a wide range of neuropathological disorders (MS, epilepsy episodes of ischemic brain disorders). IL-17A, acting on spinal nerve roots and the spinal cord, contributes to neuropathic and inflammatory pain promotion through pain receptors.Also, IL-17A is very important to damaged sympathetic axons which innervate the cornea regeneration and growth.	29736281	Details
FA2H	MS	Western blotting	Peripheral blood	down-regulation	Disease risk	The findings may suggest that impaired necroptosis is a novel mechanism of neurodegeneration, promoting a disorder that shares some clinical features with primary progressive multiple sclerosis (PPMS) and other neurodegenerative diseases	MLKL leads to a deficiency of MLKL protein resulting in impairment of necroptosis	32358523	Details
NT5E	HIVinfected、MS	ELISA	Peripheral blood	down-regulation	Disease risk	ATP-mediated downregulation of CD73 mainly occurs via its receptor, P2X1/P2RX1. Our results may in part explain why HIV-infected individuals have reduced risk of developing MS considering the role of CD73 for efficient T cell entry into the central nervous system	elevated levels of ATP in the plasma of HIV-infected individuals upregulates the expression of miRNA30b-e in T cells in vitro. In turn, inhibition of miRNAs (30b, 30c and 30e) resulted in significant upregulation of CD73 mRNA in CD8+ T cells. Therefore, we provide a novel mechanism for the downregulation of CD73 via ATP-induced upregulation of miRNA30b, 30c and 30e in HIV infection	35325005	Details
PTPRC	MS	Immunofluorescence labelling	CSF	up-regulation	Disease risk	These results suggest that V61 + and V62 + y6 T cells with altered CD45 expression are reduced in CSF of patients with established MS. This finding may be related to sequestration or apoptosis of y8 T cells within active MS lesions.	Patterns of lymphocyte recirculation in man appear to be closely related to cell surface expression of the CD45RA and CD45RO isoforms of the common leucocyte antigen CD45	7853024	Details
Tgfb1	EAE	ELISA	Peripheral blood	up-regulation	Disease risk	TGF-b1 gene delivery had pronounced downregulatory effects on T cell proliferation and production of interferon c (IFN-c ) and tumor necrosis factor a (TNF-a), on in vitro restimulation with MBP. IL-4-IgG1 vector administration also suppressed these responses, although much less than TGF-b1, and enhanced secretion of endogenous IL-4. Therapy resulted in a significant decrease in the severity of histopathologic inflammatory lesions. In the CNS, treatment with either vector suppressed IL-12 and IFN-c mRNA expression, while IL-4 and TGF-b1 mRNA levels were increased compared with control mice. Thus, cytokine plasmid treatment appeared to inhibit MBP-specific pathogenic Th1 responses, while enhancing endogenous secretion of protective cytokines. We demonstrate that gene therapy with these vectors is an effective therapeutic strategy for EAE	We studied the immunoregulatory properties of TGF-b1 and IL-4 in an animal model of EAE, by direct intramusculas injection of plasmid DNA expression vectors encoding either TGF-b1 (pVR-TGF-b1) or an IL-4–IgG1 chimeric protein (pVR-IL-4-IgG1). Treatment with either vector resulted in cytokine production capable of suppressing CNS inflammation in mice with MBP-induced EAE. Both cytokines had downregulatory effects on T cell proliferation, and production of proinflammatory cytokines, although TGF-b1 was more suppressive. As well, cytokine gene therapy enhanced the production of endogenous regulatory cytokines in lymph node cells and CNS tissue. Somatic cytokine gene therapy proved to be effective in this autoim- mune disease.	10466625	Details
Mbp	EAE	ELISA	Peripheral blood	up-regulation	Disease risk	TGF-b1 gene delivery had pronounced downregulatory effects on T cell proliferation and production of interferon c (IFN-c ) and tumor necrosis factor a (TNF-a), on in vitro restimulation with MBP. IL-4-IgG1 vector administration also suppressed these responses, although much less than TGF-b1, and enhanced secretion of endogenous IL-4. Therapy resulted in a significant decrease in the severity of histopathologic inflammatory lesions. In the CNS, treatment with either vector suppressed IL-12 and IFN-c mRNA expression, while IL-4 and TGF-b1 mRNA levels were increased compared with control mice. Thus, cytokine plasmid treatment appeared to inhibit MBP-specific pathogenic Th1 responses, while enhancing endogenous secretion of protective cytokines. We demonstrate that gene therapy with these vectors is an effective therapeutic strategy for EAE	We studied the immunoregulatory properties of TGF-b1 and IL-4 in an animal model of EAE, by direct intramusculas injection of plasmid DNA expression vectors encoding either TGF-b1 (pVR-TGF-b1) or an IL-4–IgG1 chimeric protein (pVR-IL-4-IgG1). Treatment with either vector resulted in cytokine production capable of suppressing CNS inflammation in mice with MBP-induced EAE. Both cytokines had downregulatory effects on T cell proliferation, and production of proinflammatory cytokines, although TGF-b1 was more suppressive. As well, cytokine gene therapy enhanced the production of endogenous regulatory cytokines in lymph node cells and CNS tissue. Somatic cytokine gene therapy proved to be effective in this autoim- mune disease.	10466625	Details
Trav6-3	EAE	immunizations	splenocytes	up-regulation	Disease risk	we conclude that CD41 T regulatory cells do not express canonical TCRs and that the altered signaling properties brought about by coexpression of two TCRs are not sufficient for the generation of regulatory T cells. Instead, our results indicate that regulatory T cells belong to a population displaying wide TCR diversity, but in which TCR specificity is central to their protective function	as myelin basic protein-specific/OVA-specific recombinase activating gene-12/2 double TCR transgenic mice still developed experimental autoimmune encephalomyelitis spontaneously even after immunization with OVA	10799918	Details
Tnf	MS	Western blot	brain	up-regulation	Disease risk	we demonstrate that estrogens and progesterone also inhibit NO production by microglial cells activated in response to these cytokines. Activated microglia elicit TNF-a in addition to NO and we further demonstrate that estrogens and progesterone repress TNF-a production by these cells. Finally, estriol and progesterone, at concentrations consistent with late pregnancy, inhibit NO and TNF-a production by activated microglia, suggesting that hormone inhibition of microglial cell activation may contribute to the decreased severity of multiple sclerosis symptoms commonly associated with pregnancy	These hormones act by inhibiting the production of inducible nitric oxide synthase (iNOS) which catalyses the synthesis of NO	11063824	Details
Cd4	MS	ELISA	Spinal cords	up-regulation	Disease risk	Our observations indicated that chemokine expression in the CNS in this chronic viral disorder was intrinsic to the CNS innate immune response to infection and was not governed by elements of the adaptive immune system.	resistant B6 animals were rendered TMEV-susceptible by deletion of either CD4or CD8T cells	11836399	Details
Cxcl10	EAE	Western blot	Peripheral blood	up-regulation	Disease risk	This demonstrates not only the pivotal role of a chemokine in T cell polarization and function but also its potential implications for plasmid DNA gene therapy	IFN-r inducible protein 10 (IP-10) is a CXC chemokine that stimulates the directional migration of activated T cells, particularly Th1 cells	12023393	Details
Cxcl10	EAE	Immunohistochemical analysis	brain、spleen、thymus	up-regulation	Disease risk	CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN	Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats	12115662	Details
Cxcr3	EAE	Immunohistochemical analysis	brain、spleen、thymus	up-regulation	Disease risk	CXCL10 produced in the LN plays a specific inhibitory role in the development of Th1-mediated diseases such as EAE by holding sensitized and activated Th1s expressing CXCR3 in the draining LN	Induction of gene expression of CXCL9/Mig and CXCL10 and their receptor CXCR3 was confirmed in the draining LN in EAE rats	12115662	Details
Mog	EAE	Western blot	Peripheral blood	up-regulation	Disease risk	This total lack of immune tolerance to MOG in WT C57BL/6 mice may be responsible for the high pathogenicity of the anti-MOG immune response as well as the high susceptibility of most animal strains to MOG-induced EAE	EAE is transferred to MOG+/+ recipients by either resting or primed T cells from MOG–/– and MOG+/+ mice	12925695	Details
ERVW-1	MS	Immunohistology	brain	up-regulation	Disease risk	This is compatible with a pathophysiological role in MS, but also illustrates the ambivalence of such HERV antigens, which can be expressed in cell-specific patterns, under physiological or pathological conditions	converging results from three groups confirm that GAG and ENV proteins encoded by the HERV-W multicopy gene family are expressed in cells of the central nervous system under normal conditions	15804956	Details
SPP1	MS	ELISA	Peripheral blood	up-regulation	Disease risk	These data suggest that OPN genotypes may influence MS development and progression due to their influence on OPN levels	OPN is a 60-kDa secreted phosphoprotein functioning as a free cytokine in body fluids or as an immobilized extracellular matrix molecule in mineralized tissues	15885319	Details
PTPRC	MS	Immunoprecipitation and immunoblotting	venous blood	up-regulation	Disease risk	These data suggest that 77C3G may act as a risk factor for certain diseases by increasing the intensity of TCR signaling	Mutant T cell lines contained a more active pool of p56lck tyrosine kinase and responded with increased phosphorylation of Zap70 and TCR- and an enhanced Ca2+ flux to TCR/CD3 stimulation	16393978	Details
Gm4736	EAE	ELISPOT assays and ELISPOT image analysis	Peripheral blood	up-regulation	Disease risk	In summary, the MP4-induced EAE of B6 mice bears many features seen in different neuroantigen/mouse strain combinations, all of which are hallmarks of MS. In particular the dependence on CD8+ T and B cells, the multi-determinant specificity of the CD4+ T cell response, and the rapid onset of EAE are distinct features that distinguish MP4-induced EAE from the MOG:35 – 55triggered disease of B6 mice and possibly from PLP:178– 191 peptide-induced EAE. New models will help adopt the rapidly growing array of genetically-manipulated mice for mechanism-oriented studies of immunological as well as degenerative and reparative processes as they pertain to MS.	MBP-PLP fusion protein (MP4)-induced EAE for C57BL/6 mice. B cell- and CD8+ T cell-dependence, as well as multi-determinant recognition are among the unique features of this demyelinating EAE	16781782	Details
CD200	MS	Immunohistochemistry	brain	down-regulation	Disease risk	These data suggest that diminished immune inhibition via decreased CD200 and CD47 expression contributes to a disturbed equilibrium in macrophage and microglia activation in MS lesions. Furthermore, this may result in a proinflammatory predisposition in the area surrounding chronic active lesions, thereby contributing to axonal injury, demyelination, and possible lesion expansion	The membrane glycoproteins CD200 and CD47, highly expressed on neurons, are mediators of macrophage inhibition via their receptors CD200R and signal-regulatory protein, respectively, on myeloid cells. We determined the expression pattern of immune inhibitory molecules in relation to genes involved in macrophage activation and MS lesion pathology	17879969	Details
CD47	MS	Immunohistochemistry	brain	down-regulation	Disease risk	These data suggest that diminished immune inhibition via decreased CD200 and CD47 expression contributes to a disturbed equilibrium in macrophage and microglia activation in MS lesions. Furthermore, this may result in a proinflammatory predisposition in the area surrounding chronic active lesions, thereby contributing to axonal injury, demyelination, and possible lesion expansion	The membrane glycoproteins CD200 and CD47, highly expressed on neurons, are mediators of macrophage inhibition via their receptors CD200R and signal-regulatory protein, respectively, on myeloid cells. We determined the expression pattern of immune inhibitory molecules in relation to genes involved in macrophage activation and MS lesion pathology	17879969	Details
Foxp3	EAE	Immunofluorescence	lymph nodes	down-regulation	Disease risk	Our work helps elucidate the ambiguity concerning the role of TGFβ in CD4+CD25+ Treg-mediated suppression and indicates that LAP is an authentic marker able to identify a TGFβ-expressing CD4+CD25+ Treg subset	CD4+CD25+LAP+ cells suppress myelin oligodendrocyte glycoprotein-specific immune responses by inducing Foxp3 and by inhibiting IL-17 production.	18490732	Details
Mbp	MS	Immunofluorescence	Peripheral blood	up-regulation	Disease risk	In sum, our biochemical observations led us to hypothesize that MT6-MMP, which is activated by furin and associated with the lipid rafts, plays an important role in MS pathology and that MT6-MMP is a novel and promising drug target in MS especially when compared with other individual MMPs	we demonstrated that MT6-MMP proteolysis of the MBP isoforms readily generated, with a near quantitative yield, the immunogenic N-terminal 1–15 MBP peptide. This peptide selectively stimulated the proliferation of the PGPR7.5 T cell clone isolated from mice with EAE and specific for the 1–15 MBP fragment presented in the MHC H-2U context	19300513	Details
MBP	MS	Immunostaining	Brain and Spinal	up-regulation	Disease risk	These data suggest that MMP-25 plays an important role in MS pathology and that MMP-25, especially because of its restricted cell/tissue expression pattern and cell surface/lipid raft localization, is a promising drug target in MS	We have discovered biochemical evidence suggesting the presence of the inflammatory proteolytic pathway leading to MS. The pathway involves the self-activated furin and PC2 proprotein convertases and membrane type-6 MMP (MT6-MMP/MMP25) that is activated by furin/PC2. These events are followed by MMP-25 proteolysis of the Golli-MBP isoforms in the immune system cells and stimulation of the specific autoimmune T cell clones	19726693	Details
FOXP3	MS	Immunocytochemistry	bone marrow aspirates	up-regulation	Disease risk	the reduced expression of mesodermal markers and reduced capacity for adipogenic or osteogenic differentiation in MSC-NPs compared with MSCs suggested that MSC-NPs have reduced potential of unwanted mesodermal differentiation upon CNS transplantation. The immunoregulatory function of MSC-NPs was similar to that of MSCs in their ability to suppress T-cell proliferation and to promote expansion of FoxP3-positive T regulatory cells in vitro. In addition, MSC-NPs promoted oligodendroglial differentiation from brain-derived neural stem cells that correlated with the secretion of bioactive factors. Our results provide a set of identity characteristics for autologous MSC-NPs and suggest that the in vitro immunoregulatory and trophic properties of these cells may have therapeutic value in the treatment of MS	The immunoregulatory function of MSC-NPs was similar to that of MSCs in their ability to suppress T-cell proliferation and to promote expansion of FoxP3-positive T regulatory cells in vitro	23197858	Details
Gnmt	EAE	ELISA	spinal cords	up-regulation	Disease risk	In summary, our findings suggest that GNMT is involved in the pathogenesis of EAE and plays a crucial role in the regulation of CD4+ T-cell functions	When the T-cell receptor was stimulated, the proliferative capacity and the activation status of mTOR-associated downstream signaling were decreased significantly in Gnmt–/– CD4+ T cells via an IL-2- and CD25-independent manner	25535034	Details
BACH2	MS	immunoassay	Peripheral blood	up-regulation	Disease risk	Our findings support the plausibility of the existence of common deregulated mechanisms shared by MS and HT, such as BACH2/PDCD5-FOXP3 pathways and Tregs	BACH2/PDCD5-FOXP3 pathways	29527211	Details
PDCD5	MS	immunoassay	Peripheral blood	up-regulation	Disease risk	Our findings support the plausibility of the existence of common deregulated mechanisms shared by MS and HT, such as BACH2/PDCD5-FOXP3 pathways and Tregs	BACH2/PDCD5-FOXP3 pathways	29527211	Details
FOXP3	MS	immunoassay	Peripheral blood	up-regulation	Disease risk	Our findings support the plausibility of the existence of common deregulated mechanisms shared by MS and HT, such as BACH2/PDCD5-FOXP3 pathways and Tregs	BACH2/PDCD5-FOXP3 pathways	29527211	Details
Gjc2	MS	immunoassay	Peripheral blood	up-regulation	Disease risk	These findings suggest that oligodendroglia-specific Cx47 ablation induces severe inflammation upon autoimmune demyelination, underscoring a critical role for Cx47 in regulating neuroinflammation.	CXCR3-CCR6+CD4+ and IL17+IFNγ-CD4+ helper T (Th) 17 cells isolated from spinal cord and brain tissues were significantly increased in Cx47 icKO mice compared with Cx47 fl/fl mice, while MOG35-55-specific proliferation and proinflammatory cytokine production of splenocytes were unaltered	31932428	Details
Mcu	EAE	Western blotting	spinal cord	up-regulation	Disease risk	These findings suggest that MCU inhibition contributes to axonal damage that drives MS progression	cytoskeletal damage, fragmented mitochondria and large autophagosomes were seen in EAE/Thy1-MCU Def axons	32745471	Details
ETS1	MS	ELISA	Peripheral blood、CFS	up-regulation	Disease risk	The study demonstrated the positive role of miR-1-3p in Th17 differentiation associated with MS via targeting ETS1.	MiR-1-3p overexpression in nave CD4+ T cells promoted the differentiation of Th17 cells by upregulating the level of inflammation-associated markers	32633381	Details
Ifnb1	EAE	ELISA	spleens	up-regulation	Treatment risk	Our results indicate the viability of a convenient and effective gene-based alternative for long-term IFN-B protein therapy in MS.	sustained elevation in 2V, 5V-OAS mRNA	16782409	Details
Nos2	EAE	ELISA	medulla spinalis	up-regulation	Disease risk	Increase in inflammation, the extent of myelin lesions and oxidative stress were also observed in EAE animals treated with PT.	Injection of myelin antigens stimulates the animal's immune system for proliferating and expansion of immune cells activated against the antigens. These reactive cells pass the blood–brain barrier and face the CNS parenchyma where they make inflammatory products and cytokines and destroy the myelin. They also activate microglia presented in CNS and produce factors which recruit more inflammatory components and perpetuate inflammatory cascade. B cells and their antibodies enter CNS as well and plasma cells produce some antibodies in CNS. Antibody-mediated destruction takes part in inflammatory demyelination and axonal damage	26616879	Details
IL1B	MS、EAE	ELISA	brain	up-regulation	Disease risk	Altogether, these results point to a role of IL1B and the NLRP3 inflammasome as prognostic biomarker and potential therapeutic target, respectively, in patients with primary progressive multiple sclerosis.	NF-jB pathway	32282893	Details
HHEX	MS	Western blot	peripheral blood	down-regulation	Disease risk	The present study evidenced statistically significant lower HHEX mRNA levels in lymphocytes of MS patients compared to those of controls, showing a similar trend in MS patients to the already described eQTL effect in blood from healthy individuals. Even though no differences were found in protein expression according to HHEX genotypes, statistically significant divergent subcellular distributions of HHEX appeared in patients and controls. The epistatic interaction detected between BCL6 and HHEX MS-risk variants in healthy individuals was absent in patients, indicative of a perturbed reciprocal regulation in the latter. Lymphocytes from MS carriers of the homozygous mutant genotype exhibited a distinctive, more energetic profile, both in resting and activated conditions, and significantly increased glycolytic rates in resting conditions when compared to controls sharing the HHEX genotype. In contrast, significantly higher mitochondrial mass was evidenced in homozygous mutant controls.	eIF4E-mediated mRNA transport	35887298	Details
HDAC1	EAE	Flow cytometry and cell sorting	Pooled cell suspensions of lymph nodes and spleens	down-regulation	Treatment risk	EAE susceptibility was restored in WT:HDAC1-cKO mixed BM chimeric mice, indicating a cell-autonomous defect. Our data demonstrate a novel pathophysiological role for HDAC1 in EAE and provide evidence that selective inhibition of HDAC1 might be a promising strategy for the treatment of MS	HDAC1-cKO CD4t T cells	28964722	Details