Glutamic acid decarboxylase antibody-associated neurological syndromes: Clinical and antibody characteristics and therapy response.

Background: Antibodies against glutamic acid decarboxylase (GAD-abs) at high serum levels are associated with diverse autoimmune neurological syndromes (AINS), including cerebellar ataxia, epilepsy, limbic encephalitis and stiff-person syndrome. The impact of low serum GAD-ab levels in patients with suspected AINS remains controversial. Specific intrathecal GAD-ab synthesis may serve as a marker for GAD-ab-associated nervous system autoimmunity. We present characteristics of a multicentric patient cohort with suspected AINS associated with GAD antibodies (SAINS-GAD+) and explore the relevance of serum GAD-ab levels and intrathecal GAD-ab synthesis.
Methods: All patients with SAINS-GAD+ included in the registry of the German Network for Research on Autoimmune Encephalitis (GENERATE) from 2011 to 2019 were analyzed. High serum GAD-ab levels were defined as RIA>2000 U/mL, ELISA>1000 U/mL, or as a positive staining pattern on cell-based assays.
Results: One-hundred-one patients were analyzed. In descending order they presented with epilepsy/limbic encephalitis (39%), cerebellar ataxia (28%), stiff person syndrome (22%), and overlap syndrome (12%). Immunotherapy was administered in 89% of cases with improvements in 46%. 35% of SAINS-GAD+ patients had low GAD-ab serum levels. Notably, unmatched oligoclonal bands in CSF but not in serum were more frequent in patients with low GAD-ab serum levels. GAD-ab-levels (high/low) and intrathecal GAD-ab synthesis (present or not) did not impact clinical characteristics and outcome.
Conclusions: Overall, immunotherapy in SAINS-GAD+ was moderately effective. Serum GAD-ab levels and the absence or presence of intrathecal GAD-ab synthesis did not predict clinical characteristics or outcomes in SAINS-GAD+. The detection of unmatched oligoclonal bands might outweigh low GAD-ab serum levels.
Competing Interests: Declaration of Competing Interest Madlener, Doppler, Finke, Gerner, Lewerenz, Linsa, Mues, Paliantonis, Priller, Prüß, Rössling, Schirotzek, Senel, Sommer, Strippel, Süße, Tauber, Wandinger, Wickel: Nothing to report. Fink: Bayer, Desitin, GSK, Novartis, Pfizer: lectures. Kellingshaus: UCB Pharma, Eisai GmbH, LivaNova Europe: lectures, consultancies. Kraft: Böhringer-Ingelheim, Daichii-Sankyo, Pfitzer/BMS, Bayer: travel expenses, lectures. Kümpfel: Bayer Healthcare, Merck, Novartis Pharma, Roche Pharma: lectures, consultancies. Leypoldt: Alexion, Roche and Biogen AdvisoryBoard, Novartis, Bayer, Roche: lectures. Malter: UCB Pharma, EISAI GmbH: lectures, consultancies. Melzer: Biogen Idec, GlaxoSmith Kline, Teva, Novartis Pharma, Bayer Healthcare, Genzyme, Alexion Pharamceuticals, Fresenius Medical Care, Diamed, and BIAL: lectures, Euroimmun, Fresenius Medical Care, Diamed, Alexion Pharamceuticals, and Novartis Pharma: funding. Menge: Biogen, Novartis, Teva: lectures, Biogen: consultancies, travel expenses. Ringelstein: Novartis, Bayer, Roche, Alexion, Ipsen: lectures, Bayer Schering, Biogen Idec, Merz, Genzyme, Teva, Grifols, Roche and Merck: travel expenses. Urbanek: Böhringer-Ingelheim: lectures, Daichii-Sankyo: lectures, travel expenses, sPfitzer/BMS: travel expenses. Senel: Bayer, Biogen, Merck, Roche, and Sanofi Genzyme: lectures and/or consultancies; Celgene, TEVA: travel expenses. Sühs: Merck: lectures, travel expenses. Tauber: Teva, Biogen, Merck Serono und Roche: lectures, travel expenses. Thaler: Novartis: funding. Then Bergh: Actelion, Novartis: funding; Actelion, Bayer, Merck, Roche: lectures; Merck, Roche, Sanofi-Genzyme: Advisory Board; Actelion, Merck: travel expenses.
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