In addition to tissue transglutaminase, glutamic acid decarboxylase (GAD) is another target enzyme involved in gluten sensitivity and neuroauotimmune disorders.
GAD is the enzyme responsible for the production of y-aminobutyric acid (GABA), the most abundant inhibitory neurotransmitter in the central nervous system. Antibodies against GAD have been described in stiff person syndrome, insulin-dependent diabetes mellitus (IDDM), and autoimmune polyendocrine syndromes, as well as in some immune mediated ataxias. These antibodies are present in at least 60% of both patients with gluten ataxia and patients with CD and no neurological manifestations. Furthermore, the levels and positivity of these anti-GAD antibodies can be significantly reduced by the introduction of a gluten-free diet in both of these patient groups. Of the patients with neurological manifestations, who also have an enteropathy, the prevalence of these antibodies is 96%. These observations imply that the presence of these antibodies in the context of the enteropathy might predispose individuals to the development of neurological disease. However, this cannot explain the entire story within the whole spectrum of gluten sensitivity because the antibodies arc still present in some patients with gluten-related neurological dysfunction and no enteropathy. Patients with disease processes characterized by the presence of anti-GAD antibodies also appear to have a higher prevalence of CD (e.g. patients with IDDM), stiff person syndrome and polyendocrine syndrome type II, where CD can be part of the syndrome). The prevalence of GAD within the nervous system correlated with the clinical presentation of ataxia and/ or peripheral neuropathy being the commonest neurological manifestations of gluten sensitivity.
The presence of GAD in the enteric plexus could hold the key to the generation of anti-GAD antibodies in patients with CD.38″40
Key concepts and clinical implications:
• In addition to gliadin and transglutaminase antibodies, patients with neurological symptomatologies should be tested for glutamic acid decarboxylase (GAD), myelin basic protein, neurofilaments, and cerebellar antibodies.
(Aristo Vojdani, Ph.D. – The immunology of gluten sensitivity beyond the intestinal tract)