Myasthenia gravis and autoantibodies: Pathophysiology of the different subtypes

Myasthenia gravis is characterized by muscle weakness and abnormal fatigability. It is an autoimmune disease caused by the presence of antibodies against components of the muscle membrane localized at the neuromuscular junction. In most cases, the autoantibodies are directed against the acetylcholine receptor (AChR). Recently, other targets have been described, such as muscle-specific kinase protein (MuSK) or lipoprotein related protein 4 (LRP4). The origin of the autoimmune response is not known, but thymic abnormalities and defects in immune regulation certainly play a major role in patients with anti-AChR antibodies. Genetic predisposition probably influences the occurrence of the disease. Sex hormones seem to play a role in the early form of the disease. Muscle weakness is fluctuating and worsens with exercise. Myasthenia gravis could be classified according to the location of the affected muscles (ocular versus generalized), the age of onset of symptoms, thymic abnormalities and profile of autoantibodies. These criteria are used to optimize the management and treatment of patients. In this review, we analyze the latest concepts of the pathophysiology of myasthenia gravis according to the different subgroups of the disease, including a description of the role of immunological, genetic and environmental factors. The potential viral hypothesis of this disease is discussed. Finally, we also discuss the biological assays available to validate the diagnosis. (C) 2013 Societe nationale francaise de medecine interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.