Myasthenia gravis

Myasthenia gravis (MG) is the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. It is almost invariably associated with pathological alterations of the thymus. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis B cells are increased in the medulla forming germinal centers or diffuse B cell infiltrates. Intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and involves AChR on myoid cells as the triggering (myasthenogenic) antigen. In thymomas no intratumorous immune reaction occurs and the AChR is not the myasthenogenic antigen. Instead, an abnormal neurofilament that shares epitopes with the AChR is expressed in thymomas and may trigger AChR-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of MG take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. The etiology of MG remains enigmatic.