Myasthenia Gravis and Related Disorders
Viegas S., Vincent A.
Myasthenia gravis (MG) and the Lambert-Eaton myasthenic syndrome (LEMS) are the prototypical autoimmune channelopathies of the peripheral nervous system. The predominant neuromuscular junction antigenic targets are either postsynaptic (MG; nicotinic acetylcholine receptor (AChR)) or presynaptic (LEMS; voltage-gated calcium channels (VGCCs)). Over the last 35 years the development of active immunization, passive transfer models, and use of transgenic animals has greatly enhanced our understanding of the biology of these disorders. The search for other antibodies in previously "seronegative" MG cases has led to the recognition of antibodies against clustered AChRs, muscle-specific kinase (MuSK) and low density lipoprotein receptor-related protein 4 (Lrp4). The pathogenic mechanisms that underlie these newer serological subclasses of MG are not yet fully understood, but are likely to be different from AChR antibody-mediated disease. While many still would consider MG an antibody-mediated disorder, it is well recognized that AChR-specific T lymphocytes and the thymus are critical to the autoimmune pathogenesis. In LEMS, new antibodies have been found including those against the intracellular protein SOX-1, which may help better predict those patients with a paraneoplastic disorder. This chapter aims to summarize the important clinical, immunological, and therapeutic aspects of both MG and LEMS, as well as highlighting recent developments in the field. © 2014 Elsevier Inc. All rights reserved.