165620 20240326115537.0 pmc:PMC9765394 pmc 10.1523/ENEURO.0369-22.2022 doi pmid:36446572 pmid altmetric:140461951 altmetric DZNE-2022-01753 English 610 van Casteren, Adriana C M 0 Differential modes of action of α1- and α1γ2- autoantibodies derived from patients with GABAAR encephalitis. Washington, DC 2022 Soc. article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1711446726_2079 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote Autoantibodies against central nervous system proteins are increasingly being recognized in association with neurologic disorders. Although a growing number of neural autoantibodies have been identified, a causal link between specific autoantibodies and disease symptoms remains unclear, as most studies use patient-derived CSF-containing mixtures of autoantibodies. This raises questions concerning mechanism of action and which autoantibodies truly contribute to disease progression. To address this issue, monoclonal autoantibodies were isolated from a young girl with a range of neurologic symptoms, some of which reacted with specific GABAA receptor (GABAAR) subunits, α1-subunit and α1γ2-subunit, which in this study we have characterized in detail using a combination of cellular imaging and electrophysiological techniques. These studies in neurons from wild-type mice (C57BL/6J; RRID:IMSR_JAX:000664) of mixed-sex revealed that the α1 and α1γ2 subunit-specific antibodies have differential effects on the GABAA receptor. Namely, the α1-antibody was found to directly affect GABAA receptor function on a short time scale that diminished GABA currents, leading to increased network excitability. On longer time scales those antibodies also triggered a redistribution of the GABAA receptor away from synapses. In contrast, the α1γ2-antibody had no direct effect on GABAA receptor function and could possibly mediate its effect through other actors of the immune system. Taken together, these data highlight the complexity underlying autoimmune disorders and show that antibodies can exert their effect through many mechanisms within the same disease. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 353 - Clinical and Health Care Research (POF4-353) G:(DE-HGF)POF4-353 POF4-353 POF IV 1 Dataset connected to CrossRef, PubMed, , Journals: pub.dzne.de Receptors, GABA-A NLM Chemicals GABAAR Other autoantibodies Other autoimmune encephalitis Other cortical/striatal neurons Other network excitability Other Autoantibodies NLM Chemicals gamma-Aminobutyric Acid 56-12-2 NLM Chemicals Animals MeSH Mice MeSH Receptors, GABA-A: metabolism MeSH Autoantibodies: metabolism MeSH Mice, Inbred C57BL MeSH Encephalitis MeSH gamma-Aminobutyric Acid MeSH Ackermann, Frauke P:(DE-2719)2810967 1 dzne Rahman, Kazi Atikur P:(DE-2719)9002314 2 dzne Andrzejak, Ewa P:(DE-2719)2811708 3 dzne Rosenmund, Christian 0000-0002-3905-2444 4 Kreye, Jakob P:(DE-2719)2811468 5 dzne Prüss, Harald P:(DE-2719)2810931 6 dzne Garner, Craig Curtis P:(DE-2719)2810922 7 dzne Ichkova, Aleksandra P:(DE-2719)9000590 8 Last author dzne 10.1523/ENEURO.0369-22.2022 p. ENEURO.0369-22.2022 - PERI:(DE-600)2800598-3 6 ENEURO.0369-22.2022 eNeuro 9 2022 2373-2822 OpenAccess http://pub.dzne.de/record/165620/files/DZNE-2022-01753.pdf OpenAccess pdfa http://pub.dzne.de/record/165620/files/DZNE-2022-01753.pdf?subformat=pdfa oai:pub.dzne.de:165620 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 1 P:(DE-2719)2810967 External Institute I:(DE-HGF)0 Extern 2 P:(DE-2719)9002314 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 3 P:(DE-2719)2811708 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2811468 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2810931 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 7 P:(DE-2719)2810922 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 8 P:(DE-2719)9000590 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-353 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Clinical and Health Care Research 1 2022 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2023-03-30 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2023-03-30 DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2023-03-30 DBCoverage StatID:(DE-HGF)1190 StatID Biological Abstracts 2022-11-11 Creative Commons Attribution CC BY 4.0 LIC:(DE-HGF)CCBY4 HGFVOC JCR StatID:(DE-HGF)0100 StatID ENEURO : 2021 2023-03-30 DBCoverage StatID:(DE-HGF)1030 StatID Current Contents - Life Sciences 2023-03-30 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2017-10-05T09:48:20Z WoS StatID:(DE-HGF)0113 StatID Science Citation Index Expanded 2022-11-11 DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2017-10-05T09:48:20Z DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2023-03-30 DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2023-03-30 IF < 5 StatID:(DE-HGF)9900 StatID 2023-03-30 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID DOAJ : Double blind peer review 2017-10-05T09:48:20Z Article Processing Charges StatID:(DE-HGF)0561 StatID 2022-11-11 DBCoverage StatID:(DE-HGF)0160 StatID Essential Science Indicators 2022-11-11 Fees StatID:(DE-HGF)0700 StatID 2022-11-11 I:(DE-2719)1810001 AG Garner Synaptopathy 0 I:(DE-2719)1810003 AG Prüß Autoimmune Encephalopathies 1 I:(DE-2719)1813004 AG Ackermann Astrocyte - Synapse Interactions 2 journal VDB UNRESTRICTED I:(DE-2719)1810001 I:(DE-2719)1810003 I:(DE-2719)1813004 FullTexts