GAD65 neurological autoimmunity

Muscle Nerve. 2017 Jul;56(1):15-27. doi: 10.1002/mus.25565. Epub 2017 Apr 11.


The glutamic acid decarboxylase 65-kilodalton isoform (GAD65) antibody is a biomarker of autoimmune central nervous system (CNS) disorders and, more commonly, nonneurological autoimmune diseases. Type 1 diabetes, autoimmune thyroid disease, and pernicious anemia are the most frequent GAD65 autoimmune associations. One or more of these disorders coexists in approximately 70% of patients with GAD65 neurological autoimmunity. Neurological phenotypes have CNS localization and include limbic encephalitis, epilepsy, cerebellar ataxia, and stiff-person syndrome (SPS), among others. Classic SPS is a disorder on the spectrum of CNS hyperexcitability which also includes phenotypes that are either more restricted (stiff-limb syndrome) or more widespread (progressive encephalomyelitis with rigidity and myoclonus). GAD65 antibody is not highly predictive of a paraneoplastic cause for neurological disorders, but diverse cancer types have been occasionally reported. For all phenotypes, responses to immunotherapy are variable (approximately 50% improve). GAD65 autoimmunity is important to recognize for both coexisting nonneurological autoimmune associations and potential immunotherapy-response. Muscle Nerve 56: 15-27, 2017.

Keywords: GAD65; ataxia; autoimmune; neurological; stiff-person.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoantibodies / metabolism*
  • Demyelinating Autoimmune Diseases, CNS / immunology*
  • Demyelinating Autoimmune Diseases, CNS / metabolism*
  • Glutamate Decarboxylase / immunology*
  • Humans


  • Autoantibodies
  • Glutamate Decarboxylase
  • glutamate decarboxylase 2