The immunopathogenesis of multiple sclerosis.
Multiple sclerosis (MS) is a T cell-mediated autoimmune disease that is triggered by unknown exogenous agents in subjects with a specific genetic background. Genes of the major histocompatibility complex class II region are the only ones that have been consistently associated with the disease. However, susceptibility is probably mediated by a heterogeneous array of genes, which demonstrate epistatic interactions. Furthermore, an infectious etiology of MS has been suggested, and it is likely that infectious agents shape the immune response against self-antigens. Composition of plaques, response to therapy, and data from animal models indicate that MS is mediated by myelin-specific CD4 T cells that, upon activation, invade the central nervous system and initiate the disease. Different patterns of tissue damage have been shown in active MS lesions, suggesting that the mechanisms of injury are probably distinct in different subgroups of patients. Heterogeneity in clinical characteristics, magnetic resonance imaging, and response to therapies support this notion. The experience gained during several pharmacological studies has improved our understanding of the pathogenesis of MS. New tools, such as gene expression profiling with cDNA microarrays and proteomics, together with advancements in imaging techniques may help us to identify susceptibility genes and disease markers, which may enable us to design more effective therapies and to tailor them according to different disease forms or stages.
Prat
Elisabetta
E
Neuroimmunology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1400, USA.
Martin
Roland
R
D001327:Autoimmune Diseases / Q000276:immunology / Q000503:physiopathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D007167:Immunotherapy / Q000379:methods*; D008297:Male; D008967:Molecular Biology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy*; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome