[Autoantibodies to GAD and autoimmune-mediated neurological diseases]

Nihon Rinsho. 2013 May;71(5):921-6.
[Article in Japanese]

Abstract

Autoantibodies to GAD (GAD-Ab) are associated with stiff-person syndrome and cerebellar ataxia. Recent physiological studies have clarified that GAD-Ab causes cerebellar ataxia in high-titer GAD-Ab-positive ataxia. In rat cerebellar slices, the cerebrospinal fluid (CSF) from GAD-Ab-positive ataxia acted on the terminals of GABAergic interneurons to depress the GABA release on Purkinje cells. Reduction of spill-over GABA simultaneously attenuated the inhibition of glutamate release from neighboring excitatory synapses. Such a dual synaptic impairment, the depression at GABA synapses and the potentiation at glutamate synapses, would elicit a marked excitation of Purkinje cells. These pathogenic actions were diminished by absorption of GAD-Ab using recombinant GAD. Furthermore, it is reported that intra-administration of the CSF depressed the cerebellum-mediated inhibition on motor cortex. GAD-Ab would cause neurological symptoms depending on the epitope specificity.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Animals
  • Autoantibodies / cerebrospinal fluid
  • Autoantibodies / immunology*
  • Autoimmune Diseases of the Nervous System / diagnosis
  • Autoimmune Diseases of the Nervous System / immunology*
  • Glutamate Decarboxylase / immunology*
  • Humans
  • gamma-Aminobutyric Acid / immunology

Substances

  • Autoantibodies
  • gamma-Aminobutyric Acid
  • Glutamate Decarboxylase