Major pathogenic effects of anti-MuSK antibodies in myasthenia gravis

J Neuroimmunol. 2006 Aug;177(1-2):119-31. doi: 10.1016/j.jneuroim.2006.05.017. Epub 2006 Jul 20.

Abstract

MG with anti-MuSK antibodies (MuSK+) is often characterized with muscle atrophy and excellent response to plasma exchanges. To elucidate some MuSK+ MG features, we analyzed the functional effects of anti-MuSK Abs in human TE 671 muscle cells. We found that some MuSK+ sera induced a striking inhibition of proliferation, accompanied by: 1) cell cycle arrest, 2) atrogin-1 overexpression, 3) AChR subunits, rapsyn, Rho A and cdc42 downregulation. These effects correlated to disease severity and to anti-MuSK Abs titer and vanished following PE. Altogether, these results indicate that anti-MuSK Abs could be pathogenic by contributing to the muscle atrophy in MuSK+ MG patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Autoantibodies / blood*
  • Autoantibodies / immunology*
  • Autoantibodies / pharmacology
  • Cell Cycle / drug effects
  • Cell Cycle / immunology
  • Cell Line
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle Proteins / drug effects
  • Muscle Proteins / immunology
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / physiopathology
  • Muscular Atrophy / blood
  • Muscular Atrophy / immunology
  • Muscular Atrophy / physiopathology
  • Myasthenia Gravis / blood*
  • Myasthenia Gravis / immunology*
  • Myasthenia Gravis / physiopathology
  • Neuromuscular Junction / metabolism
  • Neuromuscular Junction / physiopathology
  • Receptor Protein-Tyrosine Kinases / immunology*
  • Receptors, Cholinergic / immunology*
  • Receptors, Nicotinic / immunology
  • Receptors, Nicotinic / metabolism
  • SKP Cullin F-Box Protein Ligases / drug effects
  • SKP Cullin F-Box Protein Ligases / immunology
  • cdc42 GTP-Binding Protein / drug effects
  • cdc42 GTP-Binding Protein / metabolism
  • rhoA GTP-Binding Protein / drug effects
  • rhoA GTP-Binding Protein / metabolism

Substances

  • Autoantibodies
  • Muscle Proteins
  • Receptors, Cholinergic
  • Receptors, Nicotinic
  • peripheral membrane protein 43K
  • FBXO32 protein, human
  • SKP Cullin F-Box Protein Ligases
  • MUSK protein, human
  • Receptor Protein-Tyrosine Kinases
  • cdc42 GTP-Binding Protein
  • rhoA GTP-Binding Protein