AntiGAD

Anti-GAD refers to autoantibodies against glutamic acid decarboxylase, an enzyme that converts glutamate to gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system. There are two isoforms, GAD65 and GAD67, with most clinically relevant autoantibodies directed against GAD65.

Anti-GAD65 antibodies are most commonly associated with autoimmune type 1 diabetes mellitus and with autoimmune neurological disorders such as stiff-person syndrome (SPS), autoimmune cerebellar ataxia, and autoimmune epilepsy or limbic encephalitis. They can also be found in other autoimmune conditions and occasionally in relatives without overt disease. The antibodies target an intracellular enzyme, which suggests that their pathogenic role may reflect broader T-cell–mediated autoimmunity rather than direct antibody-driven injury, although they can serve as a useful diagnostic marker in the appropriate clinical context.

Diagnosis typically involves detection of anti-GAD antibodies in serum, and occasionally cerebrospinal fluid, by immunoassay methods such as radioimmunoassay or ELISA. In type 1 diabetes, anti-GAD65 positivity supports an autoimmune etiology, with high titers more frequently associated with neurologic syndromes.

Management depends on the associated condition. In type 1 diabetes, standard insulin-based therapy is used and anti-GAD status does not alter initial management. For neurologic disorders, immunotherapy (steroids, IVIG, plasmapheresis, rituximab) may be employed, alongside disease-specific treatments. Symptomatic therapies for SPS, such as baclofen or benzodiazepines, are common. Prognosis varies and can range from stable to persistent disabilities despite treatment.