Detection and prevalence of alpha-latrotoxin-like effects of serum from patients with Guillain-Barré syndrome

Muscle Nerve. 2002 Apr;25(4):549-58. doi: 10.1002/mus.10060.


Anti-GQ1b antibodies are associated with the Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome (GBS). In the ex vivo mouse diaphragm, anti-GQ1b-positive MFS serum induces muscle fiber twitching, a temporary dramatic increase of spontaneous quantal acetylcholine release, and transmission blockade at neuromuscular junctions (NMJs). These effects resemble those of alpha-latrotoxin (alpha-LTx) and are induced by antibody-mediated activation of complement. We developed an assay for detection of the alpha-LTx-like effect, using muscle fiber twitching as indicator. We tested 89 serum samples from GBS, MFS, and control subjects, and studied correlations with clinical signs, anti-ganglioside antibodies, micro-electrode physiology, and complement deposition at NMJs. Twitching was observed with 76% of the MFS and 10% of the GBS samples. It was associated with ophthalmoplegia and anti-GQ1b antibodies in patients, and with increased spontaneous acetylcholine release and C3c-deposition at mouse NMJs. This study strongly suggests that antibodies to GQ1b (with cross-reactivity to related gangliosides) are responsible for the alpha-LTx-like activity. The twitching assay is an efficient test for detection of this effect, and allows for screening of large numbers of samples and modifying drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies* / blood
  • Biological Assay / methods*
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • Gangliosides / immunology*
  • Humans
  • Immunohistochemistry
  • Male
  • Mice
  • Miller Fisher Syndrome / blood*
  • Miller Fisher Syndrome / immunology
  • Miller Fisher Syndrome / physiopathology
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / immunology
  • Muscle, Skeletal / physiopathology
  • Neuromuscular Junction / drug effects*
  • Neuromuscular Junction / immunology
  • Neuromuscular Junction / physiopathology
  • Observer Variation
  • Spider Venoms / toxicity*


  • Autoantibodies
  • Gangliosides
  • Spider Venoms
  • alpha-latrotoxin
  • GQ1b ganglioside