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Gene Review

MS  -  multiple sclerosis

Homo sapiens

Synonyms: MS1
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Disease relevance of MS


Psychiatry related information on MS


High impact information on MS

  • It is now clear that MS is not just a disease of the immune system, but that factors contributed by the central nervous system are equally important and must be considered in the future [10].
  • Both HLA and TCR genes have been linked to susceptibility for MS which is widely believed to be mediated by T cells that recognize an as yet unidentified autoantigen [11].
  • The major human demyelinating disease affecting the central nervous system is multiple sclerosis (MS) [11].
  • Because of the advances in the understanding and treatment of EAE, recent research in MS has been focused on the characterization of cellular immune responses against myelin components [11].
  • Overall, we observed no evidence of genetic association between the PTPRC polymorphism and MS susceptibility or disease course [12].

Chemical compound and disease context of MS


Biological context of MS


Anatomical context of MS

  • Our study provides evidence that HLA-DR2 can mediate both induced and spontaneous disease resembling MS by presenting an MBP self-peptide to T cells [2].
  • Although an autoimmune pathogenesis has been suggested, there are no conclusive data on the number of T cells autoreactive with myelin antigens in MS compared to controls [22].
  • Circulating lymphocyte populations were examined in 85 patients with multiple sclerosis (MS), 26 of whom showed exacerbations; 48 patients with other neurological diseases (OND); 14 patients suffering from psychiatric disorders; and 2 normal subjects [23].
  • We examined K(+) channels on dendritic cells (DCs), which infiltrate the brain in MS and may impact disease course [13].
  • Several studies have shown that demyelination in MS is caused by proinflammatory mediators which are released by perivascular infiltrates and/or activated glial cells [24].

Associations of MS with chemical compounds

  • In this study, the fine specificity of 29 CD4+ cytotoxic, long term, and limiting dilution TCL that had been generated against whole MBP and were derived from four MS patients and two healthy relatives was dissected using truncated and alanine-substituted peptides for the 87-106 peptide [25].
  • Immunological studies of mitoxantrone in primary progressive MS [14].
  • Administration of cytokines, including IFN-beta and Copaxone, may be important in stem cell transplantation therapies and perhaps important in the efficacy of existing MS therapies [26].
  • The mechanisms by which urinary p-cresol sulfate, possibly derived from tyrosine-SO(4), reflects progressive worsening that is disabling in MS are unknown [27].
  • Isolated cells were cultured unstimulated or stimulated with phytohemagglutinin A (PHA), lipopolysaccharide (LPS) and myelin basic protein (MBP)--a hypothetical autoantigen for MS [28].

Physical interactions of MS

  • This electron microscopical study has identified that, in vitro, the less cationic Marburg MBP isomer forms a more extended protein-lipid complex than MBP from healthy or chronic MS-afflicted individuals [29].
  • We observed a statistically significant increase in the CC genotype of IL-10 -819 and -592 SNPs coupled with a decreased frequency of the TGF-beta +915 CG genotype in our MS patients (Pc<0.05) [30].
  • In the present work, paralleling a previous one on T-cell TNF-alpha binding, we studied the effect of interferon (IFN)-beta-1b treatment on T-lymphocyte IL-6 binding in patients with relapsing-remitting MS [31].
  • The aim of the present study was to evaluate IFN-gamma binding on peripheral blood T-lymphocytes from MS patients, compared with those from healthy subjects [32].
  • In direct contrast to ferritin binding, transferrin binding in the MS tissue is present in the white matter tracts, but only in the periplaque region [33].

Enzymatic interactions of MS


Co-localisations of MS

  • Native LDL, epitopes of MDA-LDL, peptides of myelin basic protein and neutral lipid oil red O (ORO) staining were found to be co-localized within foamy macrophages in early and actively demyelinating MS plaques [36].
  • High level expression of CD1b in MS lesions was found to colocalize with the presence of GM-CSF in astrocytes [37].

Regulatory relationships of MS


Other interactions of MS

  • The variable (V) region of the T cell receptor (TCR) beta chain was examined among 83 T cell lines from both MS patients and healthy subjects that were reactive with the immunodominant region of human MBP (residues 84 to 102) or with a second immunodominant region of MBP (143 to 168) [4].
  • CD4 and HLA-DRalpha transcripts were dramatically increased in MS as compared with controls [20].
  • Nevertheless, brief amino acid motifs are shared among marmoset clones and CDR3 sequences from MS samples [21].
  • In the same population, serum antibody responses to recombinant myelin oligodendrocyte glycoprotein were comparable in MS patients and HD [41].
  • In active MS lesions, CXCL12 levels were high on astrocytes throughout lesion areas and on some monocytes/macrophages within vessels and perivascular cuffs, with lesser staining on EC [42].

Analytical, diagnostic and therapeutic context of MS

  • Such TCR structures may be used as targets for specific immunotherapy in MS [4].
  • Here we performed transcriptional profiling of 56 relevant genes in brain specimens from eight MS patients and eight normal controls by kinetic RT-PCR [20].
  • Isolated myelin from the brains of controls and patients with MS were incubated with purified Igs eluted from the brains of patients with MS or controls and degradation of MBP was assessed by quantitative electroimmunoblotting [43].
  • These findings may have important implications for understanding the pathogenesis of MS and how irradiation of potentially pathogenic T cells produces a reagent with possible therapeutic effects in T-cell vaccination (TCV) [44].
  • Based on elegant experiments in an animal model of MS, experimental allergic encephalomyelitis (EAE), a number of myelin proteins and peptides derived from these can induce inflammatory demyelinating lesions [45].


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  13. Potassium channels Kv1.3 and Kv1.5 are expressed on blood-derived dendritic cells in the central nervous system. Mullen, K.M., Rozycka, M., Rus, H., Hu, L., Cudrici, C., Zafranskaia, E., Pennington, M.W., Johns, D.C., Judge, S.I., Calabresi, P.A. Ann. Neurol. (2006) [Pubmed]
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  15. Pulse cyclophosphamide plus methylprednisolone induces myelin-antigen-specific IL-4-secreting T cells in multiple sclerosis patients. Takashima, H., Smith, D.R., Fukaura, H., Khoury, S.J., Hafler, D.A., Weiner, H.L. Clin. Immunol. Immunopathol. (1998) [Pubmed]
  16. Cryoelectron microscopy of protein-lipid complexes of human myelin basic protein charge isomers differing in degree of citrullination. Beniac, D.R., Wood, D.D., Palaniyar, N., Ottensmeyer, F.P., Moscarello, M.A., Harauz, G. J. Struct. Biol. (2000) [Pubmed]
  17. Hydrolysis of myelin basic protein by polyclonal catalytic IgGs from the sera of patients with multiple sclerosis. Polosukhina, D.I., Kanyshkova, T.G., Doronin, B.M., Tyshkevich, O.B., Buneva, V.N., Boiko, A.N., Gusev, E.I., Favorova, O.O., Nevinsky, G.A. J. Cell. Mol. Med. (2004) [Pubmed]
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  20. Transcriptional analysis of multiple sclerosis brain lesions reveals a complex pattern of cytokine expression. Baranzini, S.E., Elfstrom, C., Chang, S.Y., Butunoi, C., Murray, R., Higuchi, R., Oksenberg, J.R. J. Immunol. (2000) [Pubmed]
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  26. Human Mesenchymal Stem Cells Constitutively Express Chemokines and Chemokine Receptors That Can Be Upregulated by Cytokines, IFN-beta, and Copaxone. Croitoru-Lamoury, J., Lamoury, F.M., Zaunders, J.J., Veas, L.A., Brew, B.J. J. Interferon Cytokine Res. (2007) [Pubmed]
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