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

Humans Cerebellar Ataxia / drug therapy Glutamate Decarboxylase Autoantibodies Oligoclonal Bands Limbic Encephalitis / therapy Stiff-Person Syndrome / therapy

Autoantibodies Autoimmune encephalitis GAD GENERATE Glutamic acid decarboxylase

Journal

Journal of the neurological sciences

ISSN: 1878-5883

Titre abrégé: J Neurol Sci

Pays: Netherlands

ID NLM: 0375403

Informations de publication

Date de publication:
15 02 2023

Historique:

received: 02 06 2022

revised: 26 11 2022

accepted: 26 12 2022

pubmed: 8 1 2023

medline: 4 2 2023

entrez: 7 1 2023

Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND

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.

Identifiants

DOI: 10.1016/j.jns.2022.120540 PMID: 36608627

pubmed: 36608627

pii: S0022-510X(22)00402-6

doi: 10.1016/j.jns.2022.120540

pii:

doi:

Substances chimiques

Glutamate Decarboxylase EC 4.1.1.15

Autoantibodies 0

Oligoclonal Bands 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

120540

Informations de copyright

Déclaration de conflit d'intérêts

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.