GAD antibody – associated diseases

Glutamic Acid Decarboxylase (GAD65) Antibody

Glutamic acid decarboxylase (GAD) is a neuronal enzyme involved in the synthesis of the neurotransmitter gamma-aminobutyric acid (GABA). Antibodies directed against the 65-kd isoform of GAD (GAD65) are seen in a variety of autoimmune neurologic disorders including stiff-man (Moersch-Woltman) syndrome, autoimmune cerebellitis, brain stem encephalitis, seizure disorders, neuromyelitis optica and other myelopathies, myasthenia gravis, Lambert-Eaton syndrome, and dysautonomia.

 GAD65 antibody is also the major pancreatic islet antibody and an important serological marker of predisposition to type 1 diabetes. GAD65 autoantibody also serves as a marker of predisposition to other autoimmune disease that occur with type 1 diabetes, including thyroid disease (eg, thyrotoxicosis, Graves’ disease, Hashimoto’s thyroiditis, hypothyroidism), pernicious anemia, premature ovarian failure, Addison’s disease, (idiopathic adrenocortical failure) and vitiligo.


GAD (glutamic acid decarboxylase) antibodies are expressed in type 1 (autoimmune) diabetes , adrenal failure (Addison disease), autoimmune thyroid diseases , premature ovarian failure , myasthenia gravis, pernicious anemia , Stiff-man syndrome and a number of other disorders. An informative study recently published in Acta Neurologica Scandinavica documents the link between these conditions and gluten sensitivity . The authors state:

“The high prevalence of gluten sensitivity in patients with stiff-person syndrome (SPS) lead us to investigate the relationship between gluten sensitivity and GAD-antibody-associated diseases .”

They used ELISA assays for GAD antibodies and serological markers of gluten sensitivity that generated compelling data:

“”Six of seven (86%) patients with SPS were positive for anti-GAD…This compared with 9/90 (11%) patients with idiopathic sporadic ataxia …16/40 (40%) patients with gluten ataxia …and 6/10 patients with type 1 diabetes only…”

Note that the serological tests for gluten sensitivity are a blunt instrument—only 40% of confirmed cases of gluten ataxia were recognized. The abundance of false negatives is why the gluten gene sensitivity test is so valuable.

Additionally, the authors found that…

“The titre of anti-GAD reduced following the introduction of a gluten-free diet in patients with SPS who had serological evidence of gluten sensitivity.”

 Glutamic acid decarboxylase (GAD) …is involved in the formation of gamma aminobutyric acid (GABA) a central inhibitory neurotransmitter of the nervous system. Antibodies to GAD may impair GABA formation or inhibitory function. “

GAD (glutamic acid decarboxylase) produces GABA, the most abundant inhibitory (calming) neurotransmitter in the body. Suboptimal levels can manifest as anxiety, insomnia, hyperarousal, panic, feeling overwhelmed, disorganized attention, restlessness, worry, tension, inner excitability, inability to relax, etc.





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