GAD65 epitope mapping and search for novel autoantibodies in GAD-associated neurological disorders

- High-titer GAD antibodies can be found in a spectrum of CNS excitability disorders.
- In GAD-associated epilepsy no other co-existing autoantibodies have been described.
- GAD antibodies from various clinical syndromes were tested for epitope specificity.
- The main epitope, irrespective of syndrome, corresponded to the GAD catalytic core.
- Three patients with GAD-associated epilepsy were positive for a novel antibody.

Antibodies against Glutamic-acid-decarboxylase (GAD65) are seen in various CNS excitability disorders including stiff-person syndrome, cerebellar ataxia, encephalitis and epilepsy. To explore pathogenicity, we examined whether distinct epitope specificities or other co-existing antibodies may account for each disorder.The epitope recognized by all 27 tested patients, irrespective of clinical phenotype, corresponded to the catalytic core of GAD. No autoantibodies against known GABAergic antigens were found. In a screen for novel specificities using live hippocampal neurons, three epilepsy patients, but no other, were positive. We conclude that no GAD-specific epitope defines any neurological syndrome but other antibody specificities may account for certain phenotypes.