000268498 001__ 268498 000268498 005__ 20240403131605.0 000268498 0247_ $$2doi$$a10.1016/j.bbi.2024.01.220 000268498 0247_ $$2pmid$$apmid:38309639 000268498 0247_ $$2ISSN$$a0889-1591 000268498 0247_ $$2ISSN$$a1090-2139 000268498 0247_ $$2altmetric$$aaltmetric:159407421 000268498 037__ $$aDZNE-2024-00244 000268498 041__ $$aEnglish 000268498 082__ $$a150 000268498 1001_ $$0P:(DE-2719)9002282$$aArlt, Friederike A$$b0$$eFirst author$$udzne 000268498 245__ $$aKCNA2 IgG autoimmunity in neuropsychiatric diseases. 000268498 260__ $$aOrlando, Fla.$$bAcademic Press$$c2024 000268498 3367_ $$2DRIVER$$aarticle 000268498 3367_ $$2DataCite$$aOutput Types/Journal article 000268498 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1710419412_24479 000268498 3367_ $$2BibTeX$$aARTICLE 000268498 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000268498 3367_ $$00$$2EndNote$$aJournal Article 000268498 520__ $$aAutoantibodies 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. 000268498 536__ $$0G:(DE-HGF)POF4-353$$a353 - Clinical and Health Care Research (POF4-353)$$cPOF4-353$$fPOF IV$$x0 000268498 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de 000268498 650_7 $$2Other$$aAutoantibody 000268498 650_7 $$2Other$$aAutoimmune dementia 000268498 650_7 $$2Other$$aAutoimmune encephalitis 000268498 650_7 $$2Other$$aEpilepsy 000268498 650_7 $$2Other$$aImmunotherapy 000268498 650_7 $$2Other$$aKCNA2 000268498 650_7 $$2Other$$aKv1.2 000268498 650_7 $$2NLM Chemicals$$aAutoantibodies 000268498 650_7 $$2NLM Chemicals$$aKCNA2 protein, human 000268498 650_7 $$2NLM Chemicals$$aKv1.2 Potassium Channel 000268498 650_2 $$2MeSH$$aAnimals 000268498 650_2 $$2MeSH$$aHumans 000268498 650_2 $$2MeSH$$aMale 000268498 650_2 $$2MeSH$$aAdolescent 000268498 650_2 $$2MeSH$$aYoung Adult 000268498 650_2 $$2MeSH$$aAdult 000268498 650_2 $$2MeSH$$aMiddle Aged 000268498 650_2 $$2MeSH$$aAged 000268498 650_2 $$2MeSH$$aAged, 80 and over 000268498 650_2 $$2MeSH$$aFemale 000268498 650_2 $$2MeSH$$aAutoimmunity 000268498 650_2 $$2MeSH$$aRetrospective Studies 000268498 650_2 $$2MeSH$$aAutoantibodies 000268498 650_2 $$2MeSH$$aSeizures 000268498 650_2 $$2MeSH$$aAutoimmune Diseases of the Nervous System 000268498 650_2 $$2MeSH$$aMammals 000268498 650_2 $$2MeSH$$aKv1.2 Potassium Channel 000268498 650_2 $$2MeSH$$aEncephalitis 000268498 650_2 $$2MeSH$$aHashimoto Disease 000268498 7001_ $$aMiske, Ramona$$b1 000268498 7001_ $$0P:(DE-2719)2812697$$aMachule, Marie-Luise$$b2 000268498 7001_ $$aBroegger Christensen, Peter$$b3 000268498 7001_ $$aMindorf, Swantje$$b4 000268498 7001_ $$aTeegen, Bianca$$b5 000268498 7001_ $$aBorowski, Kathrin$$b6 000268498 7001_ $$0P:(DE-2719)9001872$$aButhut, Maria$$b7$$udzne 000268498 7001_ $$0P:(DE-2719)9001490$$aRößling, Rosa$$b8$$udzne 000268498 7001_ $$0P:(DE-2719)2812653$$aSánchez-Sendín, Elisa$$b9$$udzne 000268498 7001_ $$0P:(DE-2719)2812820$$avan Hoof, Scott$$b10$$udzne 000268498 7001_ $$0P:(DE-2719)9001947$$aCordero-Gómez, César$$b11$$udzne 000268498 7001_ $$0P:(DE-2719)9002228$$aBünger, Isabel$$b12 000268498 7001_ $$aRadbruch, Helena$$b13 000268498 7001_ $$aKraft, Andrea$$b14 000268498 7001_ $$aAyzenberg, Ilya$$b15 000268498 7001_ $$aKlausewitz, Jaqueline$$b16 000268498 7001_ $$aHansen, Niels$$b17 000268498 7001_ $$aTimäus, Charles$$b18 000268498 7001_ $$0P:(DE-2719)2812030$$aKörtvelyessy, Peter$$b19$$udzne 000268498 7001_ $$aPostert, Thomas$$b20 000268498 7001_ $$aBaur-Seack, Kirsten$$b21 000268498 7001_ $$aRost, Constanze$$b22 000268498 7001_ $$aBrunkhorst, Robert$$b23 000268498 7001_ $$aDoppler, Kathrin$$b24 000268498 7001_ $$aHaigis, Niklas$$b25 000268498 7001_ $$aHamann, Gerhard$$b26 000268498 7001_ $$aKunze, Albrecht$$b27 000268498 7001_ $$aStützer, Alexandra$$b28 000268498 7001_ $$aMaschke, Matthias$$b29 000268498 7001_ $$aMelzer, Nico$$b30 000268498 7001_ $$aRosenow, Felix$$b31 000268498 7001_ $$aSiebenbrodt, Kai$$b32 000268498 7001_ $$aStenør, Christian$$b33 000268498 7001_ $$0P:(DE-2719)2000030$$aDichgans, Martin$$b34$$udzne 000268498 7001_ $$aGeorgakis, Marios K$$b35 000268498 7001_ $$aFang, Rong$$b36 000268498 7001_ $$0P:(DE-2719)2810273$$aPetzold, Gabor C$$b37$$udzne 000268498 7001_ $$0P:(DE-2719)2811292$$aGörtler, Michael$$b38 000268498 7001_ $$0P:(DE-2719)2000058$$aZerr, Inga$$b39$$udzne 000268498 7001_ $$aWunderlich, Silke$$b40 000268498 7001_ $$aMihaljevic, Ivan$$b41 000268498 7001_ $$aTurko, Paul$$b42 000268498 7001_ $$aSchmidt Ettrup, Marianne$$b43 000268498 7001_ $$0P:(DE-HGF)0$$aBuchholz, Emilie$$b44 000268498 7001_ $$0P:(DE-2719)2814341$$aFoverskov Rasmussen, Helle$$b45$$udzne 000268498 7001_ $$0P:(DE-HGF)0$$aNasouti, Mahoor$$b46 000268498 7001_ $$aTalucci, Ivan$$b47 000268498 7001_ $$aMaric, Hans M$$b48 000268498 7001_ $$aHeinemann, Stefan H$$b49 000268498 7001_ $$0P:(DE-2719)2811033$$aEndres, Matthias$$b50$$udzne 000268498 7001_ $$agroup, DEMDAS study$$b51$$eCollaboration Author 000268498 7001_ $$aKomorowski, Lars$$b52 000268498 7001_ $$0P:(DE-2719)2810931$$aPrüss, Harald$$b53$$eLast author$$udzne 000268498 773__ $$0PERI:(DE-600)1462491-6$$a10.1016/j.bbi.2024.01.220$$gVol. 117, p. 399 - 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