Ms. Tsiortou of the University of Athens has no relevant financial relationships to disclose.)
Dr. Dalakas of the National and Kapodistrian University of Athens Medical School in Greece and Thomas Jefferson University, Philadelphia, Pennsylvania, received honorariums from Baxalta (Shire), Novartis, Pfizer, CSL, and Octapharma for consulting, serving on advisory committees, and speaking engagements.)
Dr. Graus, Emeritus Professor, Laboratory Clinical and Experimental Neuroimmunology, Institut D’Investigacions Biomédiques August Pi I Sunyer, Hospital Clinic, Spain, has no relevant financial relationships to disclose.)
The article describes the clinical phenotypes associated with anti-GAD antibodies as distinctly evolved the last decade, their underlying pathophysiology, the significance of anti-GAD antibody titers in clinical diagnosis, and the current therapeutic approaches.
Historical note and terminology
Glutamic acid decarboxylase (GAD) is a pyridoxal 5'-phosphate-dependent enzyme that catalyzes the conversion of the excitatory neurotransmitter l-glutamate to the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). The enzyme is widely expressed within the central nervous system and pancreatic beta-cells but is also found in lower amounts in the liver, kidneys, adrenal glands, ovaries, and testes (Grimaldi et al 1993). The presence of autoantibodies against GAD was first described in 1988 by Solimena and colleagues in a 49-year-old woman with stiff-person syndrome, epilepsy, and type-1 diabetes mellitus. They detected anti-GAD antibodies in both serum and cerebrospinal fluid and identified for the first time the immunostaining pattern of these antibodies, pointing out the possible immunological connection between stiff-person syndrome and type 1 diabetes mellitus. They concluded that the clinical manifestations of stiff-person syndrome are related to disruption of GABAergic pathways, a notion that it is still valid today (Solimena et al 1988).
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