Causes and Genetic Factors of Multiple Sclerosis

The causes of multiple sclerosis are unknown.

• Epidemiological studies suggest a genetic susceptibility and environment are important in the causation of multiple sclerosis.
• Although there is no single specific genetic linkage, a significant association of multiple sclerosis with HLA-A3, HLA-B7 and especially HLA-DW2 has been demonstrated in Caucasians.
• It has been suggested that the exogenous agent responsible for multiple sclerosis may be a viral agent and that exposure to this agent occurs easily in life i.e. below age of 15yrs.
• The manifestation of multiple sclerosis appear several years later and take a chronic course with remission and relapses like that in Creutzfeldt-Jacob disease.
• However, there is as yet no confirmed isolation or transmission of virus from multiple sclerosis material.
• Immunological mechanisms have been suggested by presence of lymphocytic infiltrates in central nervous system, abnormalities of immunoglobulin synthesis and cellular immune response in patients and association with cellular HLA types.
• The process may be triggered by a micro-organism such as a virus, which mimics the structure of self antigens.
• Viral antigens processed and presented to T cells by macrophages in association with HLA molecules result in proliferation and activation of T cells.
• Those activated T cells “home” into the brain, crossing the blood brain barrier with aid of enzymes and cytokines.
• These cytokines cause destruction of the myelin sheath.
• Cerebrospinal fluid of patients with multiple sclerosis if found to have increased content of antibody which is produced by only a few clones of cells.
• Understanding immuno-pathogenesis of multiple sclerosis has led to development of specific therapies aimed at intervening at different points in autoimmune process.

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