Effects of anti-glutamic acid decarboxylase antibodies associated with neurological diseases

Ann Neurol. 2007 Jun;61(6):544-51. doi: 10.1002/ana.21123.


Objective: Glutamic acid decarboxylase (GAD) catalyzes the conversion of glutamic acid into GABA. GAD autoantibodies (GAD-Ab) have been described in diabetes mellitus and in diseases involving the central nervous system such as stiff-person syndrome and cerebellar ataxia. However, the pathogenic role of GAD-Ab in neurological diseases remains a matter of debate.

Methods: Using neurophysiological and neurochemical methods, we analyzed the effects of intracerebellar and paraspinal administration of GAD-Ab in rats.

Results: Intracerebellar administration of IgG from patients with GAD-Ab and neurological involvement (IgG-GAD) blocked the potentiation of the corticomotor response normally associated with trains of repetitive peripheral nerve stimulation. When injected in the lumbar paraspinal region, IgG-GAD induced continuous motor activity with repetitive discharges, abnormal exteroceptive reflexes, and increased excitability of anterior horn neurons, as assessed by F/M ratios. Furthermore, IgG-GAD significantly reduced the N-methyl-D-aspartate-mediated production of nitric oxide in cerebellar nuclei and impaired the synaptic regulation of glutamate after N-methyl-D-aspartate administration. These effects were not observed after administration of IgG from the following groups: (1) patients with GAD-Ab, diabetes mellitus, and without neurological complications; and (2) control patients.

Interpretation: These results indicate that stiff-person syndrome and cerebellar ataxia are the direct consequence of antibody-mediated neuronal dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantibodies / blood
  • Autoantibodies / isolation & purification
  • Autoantibodies / pharmacology*
  • Cerebellum / drug effects
  • Cerebellum / immunology*
  • Cerebellum / metabolism
  • Chromatography, Affinity
  • Drug Administration Routes
  • Electric Stimulation
  • Evoked Potentials / drug effects
  • Evoked Potentials / immunology
  • Excitatory Amino Acid Agonists / pharmacology
  • Glutamate Decarboxylase / immunology*
  • Glutamic Acid / metabolism
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / isolation & purification
  • Immunoglobulin G / pharmacology*
  • Male
  • Microdialysis
  • Muscle, Skeletal / innervation
  • N-Methylaspartate / pharmacology
  • Nervous System Diseases / blood
  • Nervous System Diseases / immunology*
  • Nitric Oxide / metabolism
  • Rats
  • Sciatic Nerve / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / physiopathology


  • Autoantibodies
  • Excitatory Amino Acid Agonists
  • Immunoglobulin G
  • Nitric Oxide
  • Glutamic Acid
  • N-Methylaspartate
  • Glutamate Decarboxylase