Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture

Cells. 2019 Jul 2;8(7):671. doi: 10.3390/cells8070671.

Abstract

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ). Autoantibodies target key molecules at the NMJ, such as the nicotinic acetylcholine receptor (AChR), muscle-specific kinase (MuSK), and low-density lipoprotein receptor-related protein 4 (Lrp4), that lead by a range of different pathogenic mechanisms to altered tissue architecture and reduced densities or functionality of AChRs, reduced neuromuscular transmission, and therefore a severe fatigable skeletal muscle weakness. In this review, we give an overview of the history and clinical aspects of MG, with a focus on the structure and function of myasthenic autoantigens at the NMJ and how they are affected by the autoantibodies' pathogenic mechanisms. Furthermore, we give a short overview of the cells that are implicated in the production of the autoantibodies and briefly discuss diagnostic challenges and treatment strategies.

Keywords: AChR; Agrin; Lrp4; MuSK; autoantibodies; autoimmunity; history; immunopathogenesis; myasthenia gravis; neuromuscular junction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Agrin / immunology
  • Agrin / metabolism
  • Animals
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • Autoantigens / metabolism
  • Humans
  • LDL-Receptor Related Proteins / immunology
  • LDL-Receptor Related Proteins / metabolism
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / ultrastructure
  • Myasthenia Gravis / immunology*
  • Myasthenia Gravis / pathology
  • Neuromuscular Junction / immunology
  • Neuromuscular Junction / pathology*
  • Neuromuscular Junction / ultrastructure
  • Receptor Protein-Tyrosine Kinases / immunology
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Cholinergic / immunology
  • Receptors, Cholinergic / metabolism
  • Receptors, Nicotinic / immunology
  • Receptors, Nicotinic / metabolism

Substances

  • Agrin
  • Autoantibodies
  • Autoantigens
  • LDL-Receptor Related Proteins
  • Receptors, Cholinergic
  • Receptors, Nicotinic
  • MUSK protein, human
  • MuSK protein, mouse
  • Receptor Protein-Tyrosine Kinases