Insights into the aetiology and pathogenesis of multiple sclerosis.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, and the most common neurological disease affecting young adults. Multiple sclerosis is a clinically heterogeneous disorder. It is believed to be an autoimmune disease, with cell-mediated and humoral responses directed against myelin proteins. This hypothesis largely comes from pathological parallels with an animal model, experimental autoimmune encephalomyelitis (EAE). Autoimmunity to myelin proteins in humans may be inadvertently triggered by microbes which have structural homologies with myelin antigens (molecular mimicry). As with other autoimmune diseases, susceptibility to MS is associated with certain MHC genes/haplotypes. Full genomic screening of mutiplex families has underscored the role for MHC genes as exerting moderate but the most significant effects in susceptibility. The primary target autoantigen in MS has yet to be definitively identified, but as well as the major myelin proteins, it is now clear that minor myelin components, such as myelin oligodendrocyte glycoprotein (MOG) may play a primary role in disease initiation. This review examines the current knowledge about the aetiology and pathogenesis of MS, and the important similarities with EAE. A better understanding of the molecular mechanisms of autoimmune pathology will provide the basis for more rational immunotherapies to treat MS.
Ewing
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Neuroimmunology Laboratory, La Trobe University, Bundoora, Victoria, Australia.
Bernard
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D000328:Adult; D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D006801:Humans; D009103:Multiple Sclerosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000821:virology; D009185:Myelin Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D009185:Myelin Proteins