Multiple sclerosis: immune mechanism and update on current therapies.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) afflicting approximately 250,000 individuals in the United States. This inflammatory disease has variable clinical manifestations, ranging from a relapsing-remitting course to a chronic progressive disease. Approximately one third of MS patients have chronic progressive disease often leading to severe impairment of mobility, paralysis, poor vision, and disturbances of bladder and bowel function. Although the etiology and pathogenesis remain unknown, accumulating evidence supports the hypothesis that exposure to an as-yet-unidentified infectious agent(s) triggers an aberrant immune response against self nervous tissue in genetically susceptible individuals. The tenfold higher concordance rate for MS in monozygotic twins compared to dizygotic twins, the increased incidence of MS in women compared to men (2:1), and the familial and racial occurrence of MS provide strong evidence that genetic factors influence susceptibility to MS. The major predisposing genes in MS are the human leukocyte antigen (HLA) class II molecules, DR15 and DQw6, molecularly defined as HLA-DRB1, 1501-DQA1 0102-DQB1 0602. In certain ethnic groups, MS susceptibility is more strongly associated with other DR molecules. Environmental factors are also believed to play a role, as suggested by the unique worldwide prevalence, migration effects, and epidemiological studies. Increased serum and cerebrospinal fluid antibody titers to numerous viruses have been reported; however, there have been no confirmed studies detecting viral RNA or antigen in MS brain tissue. At the present time, no known treatment can significantly alter the progression of MS. Based on the postulate that MS is an autoimmune disease associated with abnormalities in immunoregulation, a number of different immunosuppressive and immunomodulating agents have been tested as therapeutic modalities. In this article, we review the circumstantial evidence suggesting that immune system abnormalities are associated with the disease process, and provide an update on current therapies used in MS.
Bansil
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University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA.
Cook
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Rohowsky-Kochan
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D001921:Brain / Q000473:pathology; D002986:Clinical Trials as Topic; D000939:Epitopes / Q000276:immunology; D005260:Female; D015329:Gene Rearrangement, T-Lymphocyte; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007167:Immunotherapy / Q000379:methods; D015182:Lymphatic Irradiation; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D018716:Molecular Mimicry; D009103:Multiple Sclerosis / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D004676:Myelin Basic Protein / Q000276:immunology; D014777:Virus Diseases / Q000150:complications / Q000276:immunology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; D000939:Epitopes; D006684:HLA-DR Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D004676:Myelin Basic Protein