Determination of Antibodies to GAD67 and Other Antigens in Patients with GAD65 Antibody-Associated Syndromes (P5.033)

Objectives: To determine the repertoire of antibodies in a large cohort of patients with GAD65 antibody-associated syndromes. Background: High titer antibodies against GAD65 have been described in a variety of disorders, including cerebellar ataxia (CA), stiff-person syndrome (SMS), and limbic encephalitis/seizures (LE). This variety of phenotypes has suggested that differences of GAD65-antibody titers and/or co-existing autoimmunities may be present in these patients. Methods: 109 patients with GAD65-antibody-associated syndromes (40 CA, 32 SMS and 37 LE cases) were included in the study. The presence of GAD65-antibodies was confirmed with immunohistochemistry of rat cerebellum, and ELISA or a cell-based assay (CBA). GAD67-antibodies were determined by a CBA, and antibodies to neuronal cell-surface antigens were examined with immunofluorescence with cultured hippocampal neurons and antigen-specific CBA (NMDAR, GABAaR, GABAbR, GlyR). Results: GAD67-antibodies were identified in 82/109 (75%) patients with anti-GAD65 associated syndromes. There was a correlation between the presence of higher titers of GAD65-antibodies and the presence of GAD67-antibodies (p=0.0054). All clinical phenotypes associated with a similar range of GAD65-antibody titers. In all patients the GAD65-antibodies recognized linear epitopes (visible by immunoblot). Thirteen patients had co-existing cell surface antibodies: 5 GlyR, 5 GABAaR, 1 GABAb receptor, and 1 NMDA receptor. The presence of cell surface antibodies was more frequent in patients with LE (7/37, 19%) compared with patients with CA (4/40, 10%) or SMS (2/32, 6%). Conclusions: 75% of patients with GAD65-antibody-associated syndromes have GAD67-antibodies. The association of GAD67-antibodies with LE has not been previously reported. The variety of phenotypes occurring in association with GAD65-antibodies cannot be explained by differences in GAD65-antibody titers (similar range in all phenotypes) or the presence of GAD67-antibodies. In a subset of patients with LE the clinical picture is likely related to coexisting and more relevant antibodies to cell-surface antigens. Funded by FIS PI11/01780 and PI12/00611, the NIH RO1NS077851 and Fundacio la Marato de TV3 (101530) Disclosure: Dr. Gresa-Arribas has nothing to disclose. Dr. Arino has nothing to disclose. Dr. Sabater has nothing to disclose. Dr. Caballero has nothing to disclose. Dr. Alba has nothing to disclose. Dr. Martinez-Hernandez has nothing to disclose. Dr. Petit has nothing to disclose. Dr. Saiz has received personal compensation for activities with Bayer Schering, Merck Serono, Biogen Idec, Sanofi-Aventis Pharmaceuticals Inc., Teva Neuroscience, and Novartis. Dr. Dalmau has received personal compensation in an editorial capacity for Up To Date. Dr. Dalmau has received royalty payments from Athena Diagnostics. Dr. Dalmau has received research support from Euroimmun. Dr. Graus has nothing to disclose.