Myasthenia gravis induced by autoantibodies against MuSK

Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission mediated by autoantibodies. That is, the binding of autoantibodies to postsynaptic membranes in neuromuscular junctions (NMJ) results in weakening of the ocular, bulbar and limb muscles and produces the characteristic syndrome of MG. This relatively rare disease serves as a model not only for study of the pathogenesis and treatment of all autoimmune disorders but also for understanding the basic mechanisms of neuromuscular transmission at the NMJ. About 80 to 85% of patients with MG have autoantibodies against acetylcholine receptors (AChR). Although a number of studies have shown the possible existence of other autoantibodies in the remaining approximately 20% of MG patients, the responsible autoantigens have remained elusive. However, antibodies against muscle-specific kinase (MuSK) have been found in 30% of MG patients without AChR antibodies. MuSK, a tyrosine kinase receptor, is required for the development of NMJ's postsynaptic membranes. Still, the pathogenicity of MuSK antibodies as a cause of muscle weakness in patients with MG remains a matter of dispute, because the experimental autoimmune MG caused by MuSK antibodies in animals was absent. Here we describe recent progress toward understanding the pathogenic role of MuSK antibodies in the decline of muscle strength that typifies MG.