Combined pre- and postsynaptic action of IgG antibodies in Miller Fisher syndrome

Neurology. 2001 Jan 9;56(1):67-74. doi: 10.1212/wnl.56.1.67.

Abstract

Background: Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome, is associated with the presence of neuromuscular blocking antibodies, some of which may be directed at the ganglioside GQ1b.

Materials and methods: The authors investigated the in vitro effects of serum and purified immunoglobulin (Ig) G in a total of 11 patients with typical MFS during active disease, and in three of those patients after recovery. From one patient's serum, we prepared an IgG fraction enriched in anti-GQ1b antibodies by affinity chromatography. For combined pre- and postsynaptic analysis, endplate currents were recorded by a perfused macro-patch clamp electrode. Postsynaptic nicotinic acetylcholine receptor channels were investigated by an outside-out patch clamp technique in cultured mouse myotubes.

Results: AllMFS-sera depressed evoked quantal release and reduced the amplitude of postsynaptic currents. Five of the 11 sera were additionally examined by outside-out patch clamp analysis and caused a concentration-dependent and reversible decrease in acetylcholine-induced currents. The time course of activation and desensitization of nicotinic acetylcholine receptor channels was not altered by MFS-IgG. Nine patients (82 %) were positive for anti-GQ1b antibodies in ELISA and dot-blot. The enriched anti-GQ1b antibody fraction had a similar effect as whole serum. After recovery from MFS, blocking activity was lost and sera originally positive for anti-GQ1b antibodies became negative.

Conclusion: Circulating IgG antibodies induce both pre- and postsynaptic blockade and may play a pathogenic role in acute MFS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Aged
  • Animals
  • Autoantibodies / immunology*
  • Autoantibodies / isolation & purification
  • Autoantibodies / pharmacology
  • Cells, Cultured
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / immunology
  • Female
  • Gangliosides / immunology
  • Humans
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / isolation & purification
  • Immunoglobulin G / pharmacology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Miller Fisher Syndrome / immunology*
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / physiology
  • Neurotransmitter Agents / metabolism
  • Patch-Clamp Techniques
  • Receptors, Nicotinic / immunology
  • Receptors, Nicotinic / metabolism
  • Synapses / immunology*
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / immunology
  • Vasodilator Agents / pharmacology

Substances

  • Autoantibodies
  • Gangliosides
  • Immunoglobulin G
  • Neurotransmitter Agents
  • Receptors, Nicotinic
  • Vasodilator Agents
  • GQ1b ganglioside
  • Acetylcholine