% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Arlt:268498, author = {Arlt, Friederike A and Miske, Ramona and Machule, Marie-Luise and Broegger Christensen, Peter and Mindorf, Swantje and Teegen, Bianca and Borowski, Kathrin and Buthut, Maria and Rößling, Rosa and Sánchez-Sendín, Elisa and van Hoof, Scott and Cordero-Gómez, César and Bünger, Isabel and Radbruch, Helena and Kraft, Andrea and Ayzenberg, Ilya and Klausewitz, Jaqueline and Hansen, Niels and Timäus, Charles and Körtvelyessy, Peter and Postert, Thomas and Baur-Seack, Kirsten and Rost, Constanze and Brunkhorst, Robert and Doppler, Kathrin and Haigis, Niklas and Hamann, Gerhard and Kunze, Albrecht and Stützer, Alexandra and Maschke, Matthias and Melzer, Nico and Rosenow, Felix and Siebenbrodt, Kai and Stenør, Christian and Dichgans, Martin and Georgakis, Marios K and Fang, Rong and Petzold, Gabor C and Görtler, Michael and Zerr, Inga and Wunderlich, Silke and Mihaljevic, Ivan and Turko, Paul and Schmidt Ettrup, Marianne and Buchholz, Emilie and Foverskov Rasmussen, Helle and Nasouti, Mahoor and Talucci, Ivan and Maric, Hans M and Heinemann, Stefan H and Endres, Matthias and Komorowski, Lars and Prüss, Harald}, collaboration = {group, DEMDAS study}, title = {{KCNA}2 {I}g{G} autoimmunity in neuropsychiatric diseases.}, journal = {Brain, behavior and immunity}, volume = {117}, issn = {0889-1591}, address = {Orlando, Fla.}, publisher = {Academic Press}, reportid = {DZNE-2024-00244}, pages = {399 - 411}, year = {2024}, abstract = {Autoantibodies against the potassium voltage-gated channel subfamily A member 2 (KCNA2) have been described in a few cases of neuropsychiatric disorders, but their diagnostic and pathophysiological role is currently unknown, imposing challenges to medical practice.We retrospectively collected comprehensive clinical and paraclinical data of 35 patients with KCNA2 IgG autoantibodies detected in cell-based and tissue-based assays. Patients' sera and cerebrospinal fluid (CSF) were used for characterization of the antigen, clinical-serological correlations, and determination of IgG subclasses.KCNA2 autoantibody-positive patients (n = 35, median age at disease onset of 65 years, range of 16-83 years, 74 $\%$ male) mostly presented with cognitive impairment and/or epileptic seizures but also ataxia, gait disorder and personality changes. Serum autoantibodies belonged to IgG3 and IgG1 subclasses and titers ranged from 1:32 to 1:10,000. KCNA2 IgG was found in the CSF of 8/21 (38 $\%)$ patients and in the serum of 4/96 (4.2 $\%)$ healthy blood donors. KCNA2 autoantibodies bound to characteristic anatomical areas in the cerebellum and hippocampus of mammalian brain and juxtaparanodal regions of peripheral nerves but reacted exclusively with intracellular epitopes. A subset of four KCNA2 autoantibody-positive patients responded markedly to immunotherapy alongside with conversion to seronegativity, in particular those presenting an autoimmune encephalitis phenotype and receiving early immunotherapy. An available brain biopsy showed strong immune cell invasion. KCNA2 autoantibodies occurred in less than 10 $\%$ in association with an underlying tumor.Our data suggest that KCNA2 autoimmunity is clinically heterogeneous. Future studies should determine whether KCNA2 autoantibodies are directly pathogenic or develop secondarily. Early immunotherapy should be considered, in particular if autoantibodies occur in CSF or if clinical or diagnostic findings suggest ongoing inflammation. Suspicious clinical phenotypes include autoimmune encephalitis, atypical dementia, new-onset epilepsy and unexplained epileptic seizures.}, keywords = {Animals / Humans / Male / Adolescent / Young Adult / Adult / Middle Aged / Aged / Aged, 80 and over / Female / Autoimmunity / Retrospective Studies / Autoantibodies / Seizures / Autoimmune Diseases of the Nervous System / Mammals / Kv1.2 Potassium Channel / Encephalitis / Hashimoto Disease / Autoantibody (Other) / Autoimmune dementia (Other) / Autoimmune encephalitis (Other) / Epilepsy (Other) / Immunotherapy (Other) / KCNA2 (Other) / Kv1.2 (Other) / Autoantibodies (NLM Chemicals) / KCNA2 protein, human (NLM Chemicals) / Kv1.2 Potassium Channel (NLM Chemicals)}, cin = {AG Prüß / AG Dichgans / AG Endres / AG Düzel / AG Petzold ; AG Petzold / AG Zerr}, ddc = {150}, cid = {I:(DE-2719)1810003 / I:(DE-2719)5000022 / I:(DE-2719)1811005 / I:(DE-2719)5000006 / I:(DE-2719)1013020 / I:(DE-2719)1440011-1}, pnm = {353 - Clinical and Health Care Research (POF4-353)}, pid = {G:(DE-HGF)POF4-353}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:38309639}, doi = {10.1016/j.bbi.2024.01.220}, url = {https://pub.dzne.de/record/268498}, }