Characteristics of myasthenia gravis with antibodies to muscle-specific kinase and low-density lipoprotein-related receptor protein 4

Abstract

Myasthenia gravis (MG) is characterized by fatigable weakness of voluntary muscles caused by immunoglobulin G autoantibodies binding to post-synaptic proteins at the neuromuscular junction. Antibodies specific for the acetylcholine receptor are detected in the great majority (85%) of MG patients. Serum immunoglobulin G binding to the muscle-specific kinase (MuSK) are found in approximately 40% of anti-acetylcholine receptor-negative patients. Recently, the low-density lipoprotein receptor-related protein 4 (Lrp4), which is the MuSK co-receptor for agrin, has been recognized as a new antigen in MG. Specific antibodies bind to the extracellular domains of MuSK and Lrp4 and, as experimental models have shown, interfere with the protein function. The present review describes the MuSK-Lrp4 complex, and summarizes the effects of MuSK and Lrp4 antibodies at the neuromuscular junction. Furthermore, the epidemiological and clinical characteristics, the response to therapy and the controversies in management of the specific diseases are discussed.