Stiff person-syndrome IgG affects presynaptic GABAergic release mechanisms

J Neural Transm (Vienna). 2015 Mar;122(3):357-62. doi: 10.1007/s00702-014-1268-1. Epub 2014 Jul 3.

Abstract

The majority of patients with stiff person-syndrome (SPS) are characterized by autoantibodies to glutamate decarboxylase 65 (GAD65). In previous passive-transfer studies, SPS immunoglobulin G (IgG) induced SPS core symptoms. We here provide evidence that SPS-IgG causes a higher frequency of spontaneous vesicle fusions. Sustained GABAergic transmission and presynaptic GABAergic vesicle pool size remained unchanged. Since these findings cannot be attributed to anti-GAD65 autoantibodies alone, we propose that additional autoantibodies with so far undefined antigen specificity might affect presynaptic release mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Embryo, Mammalian
  • Female
  • GABAergic Neurons / cytology*
  • GABAergic Neurons / drug effects
  • Glutamate Decarboxylase / immunology*
  • Hippocampus / cytology
  • Humans
  • Immunoglobulin G / pharmacology*
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects*
  • Inhibitory Postsynaptic Potentials / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microscopy, Confocal
  • Neurotransmitter Agents / pharmacology
  • Patch-Clamp Techniques
  • Presynaptic Terminals / drug effects*
  • Presynaptic Terminals / metabolism
  • Statistics, Nonparametric
  • Stiff-Person Syndrome / immunology
  • Stiff-Person Syndrome / metabolism*
  • Synaptophysin / metabolism
  • Vesicular Inhibitory Amino Acid Transport Proteins / metabolism

Substances

  • Immunoglobulin G
  • Neurotransmitter Agents
  • Synaptophysin
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2