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These autoantibodies interfere with inhibitory signal transmission, which causes a variety of symptoms. How the underlying autoantibody associated pathomechanisms contribute to the variability of clinical presentations, is so far not understood. In this study, binding patterns of GlyR autoantibodies from patients with SPS, PERM and epilepsy to murine central nervous system (CNS) tissue samples were analyzed for disease- and patient-specificity patterns. Twelve GlyR autoantibody positive patients were grouped by the patients\u2019 primary diagnoses. Serum samples from these SPS, PERM and epilepsy patients were evaluated for autoantibody binding on transfected HEK-293 cells and murine spinal cord and various brain tissue samples. Autoantibody binding was further verified by co-localization with commercial antibodies binding to the GlyR and the synaptic marker synaptophysin. Immunochemistry revealed GlyR\u03b11-specific autoantibody binding for all included patients on transfected HEK-293 cells and in the grey matter of murine spinal cord sections. Other CNS regions of enhanced autoantibody accumulation however varied among the groups of SPS, PERM and epilepsy patients and also within groups. Similarly, autoantibody deposits were detected in GlyR expressing higher brain areas for each patient. Even if variations between labeled areas and cell layers were rather patient-specific than group-specific, functionality of the labeled areas aligned with the patients\u2019 impaired functions. Labeled areas and cell layers differing between patients could thereby explain the variability of symptomatology between and within the diseases. The observed diversity suggests a necessity for a personalized approach correlating patient-specific autoantibody properties, phenotype and treatment approaches.<\/jats:p>","DOI":"10.1186\/s40478-025-02082-0","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T02:52:40Z","timestamp":1753930360000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Binding patterns of glycine receptor autoantibodies are related to clinical syndromes"],"prefix":"10.1186","volume":"13","author":[{"given":"Inken","family":"Piro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Lena","family":"Wiessler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Kakavela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bet\u00fcl","family":"Baykan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdem","family":"T\u00fcz\u00fcn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Villmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Sommer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"2082_CR1","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1186\/s12974-020-01941-y","volume":"17","author":"YM Arenas","year":"2020","unstructured":"Arenas YM, Cabrera-Pastor A, Juciute N, Mora-Navarro E, Felipo V (2020) Blocking Glycine receptors reduces neuroinflammation and restores neurotransmission in cerebellum through ADAM17-TNFR1-NF-kappabeta pathway. 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Animals: Breeding of wildtype mouse strains and the use of their tissue samples in in vitro studies was approved by local veterinary authority (Veterin\u00e4ramt der Stadt W\u00fcrzburg, Germany) and the Bavarian State Authorities (Regierung von Unterfranken, W\u00fcrzburg, Germany; license numbers: FBVVL 568\/200\u2013324\/13).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"166"}}