气候变化领域集成服务门户(CCPortal): Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis

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DOI	10.1073/pnas.1916337118
	Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis
	Brändle S.M.; Cerina M.; Weber S.; Held K.; Menke A.F.; Alcalá C.; Gebert D.; Herrmann A.M.; Pellkofer H.; Gerdes L.A.; Bittner S.; Leypoldt F.; Teegen B.; Komorowski L.; Kümpfel T.; Hohlfeld R.; Meuth S.G.; Casanova B.; Melzer N.; Beltrán E.; Dornmair K.
发表日期	2021
ISSN	00278424
卷号	118 期号:9
英文摘要	Encephalitis associated with antibodies against the neuronal gamma-aminobutyric acid A receptor (GABAA-R) is a rare form of autoimmune encephalitis. The pathogenesis is still unknown but autoimmune mechanisms were surmised. Here we identified a strongly expanded B cell clone in the cerebrospinal fluid of a patient with GABAA-R encephalitis. We expressed the antibody produced by it and showed by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry that it recognizes the GABAA-R. Patch-clamp recordings revealed that it tones down inhibitory synaptic transmission and causes increased excitability of hippocampal CA1 pyramidal neurons. Thus, the antibody likely contributed to clinical disease symptoms. Hybridization to a protein array revealed the cross-reactive protein LIM-domain-only protein 5 (LMO5), which is related to cell-cycle regulation and tumor growth. We confirmed LMO5 recognition by immunoprecipitation and ELISA and showed that cerebrospinal fluid samples from two other patients with GABAA-R encephalitis also recognized LMO5. This suggests that cross-reactivity between GABAA-R and LMO5 is frequent in GABAA-R encephalitis and supports the hypothesis of a paraneoplastic etiology. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Autoantibody; Autoimmune encephalitis; Epilepsy; GABA-A-receptor encephalitis; Paraneoplastic encephalitis
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180498
作者单位	Institute of Clinical Neuroimmunology, Biomedical Center Hospital, Ludwig-Maximilians-Universität München, Martinsried, D-82152, Germany; Department of Neurology, Institute of Translational Neurology, University of Münster, Münster, D-48149, Germany; Division of Infectious Diseases and Tropical Medicine, University Hospital, Ludwig Maximilian University of Munich, Munich, D-80539, Germany; German Centre for Infection Research (DZIF), Munich, D-80937, Germany; Neuroimmunology Unit, Hospital Universitari i Politècnic la Fe, Valencia, 46026, Spain; Department of Neurology, University of Mainz, Mainz, D-55131, Germany; Institute of Clinical Chemistry, University of Kiel, Kiel, D-24105, Germany; Department of Neurology, University of Kiel, Kiel, D-24105, Germany; Clinical-Immunological Laboratory Prof. Dr. Stöcker, Lübeck, D-23560, Germany; Institute for Experimental Immunology, Euroimmun AG, Lübeck, D-23560, Germany; Munich Cluster for Systems Neurology (SyNergy), Ludwig-Maximilians-Universität München, Münch...
推荐引用方式 GB/T 7714	Brändle S.M.,Cerina M.,Weber S.,et al. Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis[J],2021,118(9).
APA	Brändle S.M..,Cerina M..,Weber S..,Held K..,Menke A.F..,...&Dornmair K..(2021).Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis.Proceedings of the National Academy of Sciences of the United States of America,118(9).
MLA	Brändle S.M.,et al."Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis".Proceedings of the National Academy of Sciences of the United States of America 118.9(2021).