{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T19:21:37Z","timestamp":1792178497899,"version":"4.4.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T00:00:00Z","timestamp":1745539200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Novartis Foundation for Biomedical Research Young Investigator Grant"},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["PCEFP3_194609"],"award-info":[{"award-number":["PCEFP3_194609"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["32NE30_198552, CRSII5_209510, 32003B_212466, 324730_192755 and 32NE30_221732"],"award-info":[{"award-number":["32NE30_198552, CRSII5_209510, 32003B_212466, 324730_192755 and 32NE30_221732"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_179531"],"award-info":[{"award-number":["320030_179531"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["310030_215050"],"award-info":[{"award-number":["310030_215050"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National MS Society","award":["FG-1708-28871"],"award-info":[{"award-number":["FG-1708-28871"]}]},{"DOI":"10.13039\/501100023177","name":"Fondation Pierre Mercier pour la Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100023177","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Propatient Foundation"},{"name":"Goldschmidt Jacobson Foundation"},{"name":"Gottfried and Julia Bangerter Rhyner Foundation"},{"name":"ERA-NET NEURON JTC-2023 ELSA: BrainTree"},{"name":"ERA-NET NEURON JTC-2020 iSEE"},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-18-RHUS-0012"],"award-info":[{"award-number":["ANR-18-RHUS-0012"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["865026"],"award-info":[{"award-number":["865026"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006389","name":"University of Geneva","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006389","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Neuropathol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Autoimmune encephalitis (AE) is an inflammatory syndrome of the central nervous system (CNS) triggered by aberrant immune responses against neuronal intracellular (IC-AE) or surface (NS-AE) autoantigens. The resulting neuronal alterations and clinical trajectories differ, with IC-AE often leading to fatal outcomes. Unfortunately, the scarce availability of tissue from AE cases has hampered systematic analyses that would allow an understanding of the pathogenesis underlying neuronal alterations in T cell-mediated AE syndromes. Here, we assembled a cohort comprising both NS-AE (n\u2009=\u20098) and IC-AE (n\u2009=\u200912) from multiple institutions to delineate key histopathological features that distinguish neuronal pathology between IC-AE and NS-AE. In contrast to NS-AE, IC-AE lesions present a prominent neuronal pSTAT1 signature, accompanied by a high proportion of brain-resident memory CD8\u2009+\u2009T cells and neurodegenerative GPNMB\u2009+\u2009phagocytes which show synaptic engulfment with little C3-complement deposition. Our findings highlight distinct histopathological features of IC-AE compared to NS-AE, providing actionable biomarkers for diagnostics and treatment strategies.<\/jats:p>","DOI":"10.1007\/s00401-025-02882-7","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T02:50:54Z","timestamp":1745549454000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens"],"prefix":"10.1007","volume":"149","author":[{"given":"Giovanni","family":"Di Liberto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristof","family":"Egervari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Vogrig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Spatola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margot","family":"Piccinno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilena","family":"Vincenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Kreutzfeldt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Verena","family":"Endmayr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karoline","family":"Ostertag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Rahimi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Vicino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Katrin","family":"Pr\u00f6bstel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Meyronet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Frank","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Prinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Hewer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Philippe","family":"Brouland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"de Leval","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Parkkinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Draganski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginie","family":"Desestret","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divyanshu","family":"Dubey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean J.","family":"Pittock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanu F.","family":"Roemer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis W.","family":"Dickson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romana","family":"H\u00f6ftberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarosh R.","family":"Irani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e9r\u00f4me","family":"Honnorat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Du Pasquier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doron","family":"Merkler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,25]]},"reference":[{"key":"2882_CR1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1016\/S2215-0366(19)30001-X","volume":"6","author":"A Al-Diwani","year":"2019","unstructured":"Al-Diwani A, Handel A, Townsend L, Pollak T, Leite MI, Harrison PJ et al (2019) The psychopathology of NMDAR-antibody encephalitis in adults: a systematic review and phenotypic analysis of individual patient data. Lancet Psychiatry 6:235\u2013246. https:\/\/doi.org\/10.1016\/S2215-0366(19)30001-X","journal-title":"Lancet Psychiatry"},{"key":"2882_CR2","doi-asserted-by":"publisher","first-page":"4306","DOI":"10.1093\/brain\/awad238","volume":"146","author":"T Armangue","year":"2023","unstructured":"Armangue T, Olive-Cirera G, Martinez-Hernandez E, Rodes M, Peris-Sempere V, Guasp M et al (2023) Neurologic complications in herpes simplex encephalitis: clinical, immunological and genetic studies. Brain 146:4306\u20134319. https:\/\/doi.org\/10.1093\/brain\/awad238","journal-title":"Brain"},{"key":"2882_CR3","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/S1474-4422(18)30244-8","volume":"17","author":"T Armangue","year":"2018","unstructured":"Armangue T, Spatola M, Vlagea A, Mattozzi S, Carceles-Cordon M, Martinez-Heras E et al (2018) Frequency, symptoms, risk factors, and outcomes of autoimmune encephalitis after herpes simplex encephalitis: a prospective observational study and retrospective analysis. Lancet Neurol 17:760\u2013772. https:\/\/doi.org\/10.1016\/S1474-4422(18)30244-8","journal-title":"Lancet Neurol"},{"key":"2882_CR4","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1016\/j.neuroimage.2005.02.018","volume":"26","author":"J Ashburner","year":"2005","unstructured":"Ashburner J, Friston KJ (2005) Unified segmentation. Neuroimage 26:839\u2013851. https:\/\/doi.org\/10.1016\/j.neuroimage.2005.02.018","journal-title":"Neuroimage"},{"key":"2882_CR5","doi-asserted-by":"publisher","first-page":"197","DOI":"10.3389\/fnins.2012.00197","volume":"6","author":"J Ashburner","year":"2012","unstructured":"Ashburner J, Ridgway GR (2012) Symmetric diffeomorphic modeling of longitudinal structural MRI. Front Neurosci 6:197. https:\/\/doi.org\/10.3389\/fnins.2012.00197","journal-title":"Front Neurosci"},{"key":"2882_CR6","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1093\/brain\/aws082","volume":"135","author":"CG Bien","year":"2012","unstructured":"Bien CG, Vincent A, Barnett MH, Becker AJ, Blumcke I, Graus F et al (2012) Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis. Brain 135:1622\u20131638. https:\/\/doi.org\/10.1093\/brain\/aws082","journal-title":"Brain"},{"key":"2882_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1136\/practneurol-2021-003073","volume":"22","author":"S Binks","year":"2022","unstructured":"Binks S, Uy C, Honnorat J, Irani SR (2022) Paraneoplastic neurological syndromes: a practical approach to diagnosis and management. Pract Neurol 22:19\u201331. https:\/\/doi.org\/10.1136\/practneurol-2021-003073","journal-title":"Pract Neurol"},{"key":"2882_CR8","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/s41583-018-0057-5","volume":"19","author":"O Butovsky","year":"2018","unstructured":"Butovsky O, Weiner HL (2018) Microglial signatures and their role in health and disease. Nat Rev Neurosci 19:622\u2013635. https:\/\/doi.org\/10.1038\/s41583-018-0057-5","journal-title":"Nat Rev Neurosci"},{"key":"2882_CR9","doi-asserted-by":"publisher","first-page":"fcac196","DOI":"10.1093\/braincomms\/fcac196","volume":"4","author":"NL Ciano-Petersen","year":"2022","unstructured":"Ciano-Petersen NL, Muniz-Castrillo S, Birzu C, Vogrig A, Farina A, Villagran-Garcia M et al (2022) Cytokine dynamics and targeted immunotherapies in autoimmune encephalitis. Brain Commun 4:fcac196. https:\/\/doi.org\/10.1093\/braincomms\/fcac196","journal-title":"Brain Commun"},{"key":"2882_CR10","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1093\/brain\/awad419","volume":"147","author":"J Cleaver","year":"2024","unstructured":"Cleaver J, Jeffery K, Klenerman P, Lim M, Handunnetthi L, Irani SR et al (2024) The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity. Brain 147:1130\u20131148. https:\/\/doi.org\/10.1093\/brain\/awad419","journal-title":"Brain"},{"key":"2882_CR11","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/nrn.2015.27","volume":"17","author":"SJ Crisp","year":"2016","unstructured":"Crisp SJ, Kullmann DM, Vincent A (2016) Autoimmune synaptopathies. Nat Rev Neurosci 17:103\u2013117. https:\/\/doi.org\/10.1038\/nrn.2015.27","journal-title":"Nat Rev Neurosci"},{"key":"2882_CR12","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/S1474-4422(23)00083-2","volume":"22","author":"J Dalmau","year":"2023","unstructured":"Dalmau J, Graus F (2023) Diagnostic criteria for autoimmune encephalitis: utility and pitfalls for antibody-negative disease. Lancet Neurol 22:529\u2013540. https:\/\/doi.org\/10.1016\/S1474-4422(23)00083-2","journal-title":"Lancet Neurol"},{"key":"2882_CR13","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awac102","author":"G Di Liberto","year":"2022","unstructured":"Di Liberto G, Egervari K, Kreutzfeldt M, Schurch CM, Hewer E, Wagner I et al (2022) Neurodegenerative phagocytes mediate synaptic stripping in Neuro-HIV. Brain. https:\/\/doi.org\/10.1093\/brain\/awac102","journal-title":"Brain"},{"issue":"458\u2013471","key":"2882_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.049","volume":"175","author":"G Di Liberto","year":"2018","unstructured":"Di Liberto G, Pantelyushin S, Kreutzfeldt M, Page N, Musardo S, Coras R et al (2018) Neurons under T cell attack coordinate phagocyte-mediated synaptic stripping. Cell 175(458\u2013471):e419. https:\/\/doi.org\/10.1016\/j.cell.2018.07.049","journal-title":"Cell"},{"key":"2882_CR15","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/S1474-4422(24)00074-7","volume":"23","author":"A Easton","year":"2024","unstructured":"Easton A (2024) A call for awareness in encephalitis. Lancet Neurol 23:337\u2013338. https:\/\/doi.org\/10.1016\/S1474-4422(24)00074-7","journal-title":"Lancet Neurol"},{"key":"2882_CR16","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1093\/brain\/awaa117","volume":"143","author":"NL Fransen","year":"2020","unstructured":"Fransen NL, Hsiao CC, van der Poel M, Engelenburg HJ, Verdaasdonk K, Vincenten MCJ et al (2020) Tissue-resident memory T cells invade the brain parenchyma in multiple sclerosis white matter lesions. Brain 143:1714\u20131730. https:\/\/doi.org\/10.1093\/brain\/awaa117","journal-title":"Brain"},{"key":"2882_CR17","doi-asserted-by":"publisher","first-page":"832","DOI":"10.1016\/j.celrep.2017.12.066","volume":"22","author":"BA Friedman","year":"2018","unstructured":"Friedman BA, Srinivasan K, Ayalon G, Meilandt WJ, Lin H, Huntley MA et al (2018) Diverse brain myeloid expression profiles reveal distinct microglial activation states and aspects of Alzheimer\u2019s disease not evident in mouse models. Cell Rep 22:832\u2013847. https:\/\/doi.org\/10.1016\/j.celrep.2017.12.066","journal-title":"Cell Rep"},{"key":"2882_CR18","doi-asserted-by":"publisher","first-page":"eabl6157","DOI":"10.1126\/scitranslmed.abl6157","volume":"14","author":"D Frieser","year":"2022","unstructured":"Frieser D, Pignata A, Khajavi L, Shlesinger D, Gonzalez-Fierro C, Nguyen XH et al (2022) Tissue-resident CD8(+) T cells drive compartmentalized and chronic autoimmune damage against CNS neurons. Sci Transl Med 14:eabl6157. https:\/\/doi.org\/10.1126\/scitranslmed.abl6157","journal-title":"Sci Transl Med"},{"key":"2882_CR19","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1038\/s41593-019-0427-y","volume":"22","author":"C Garber","year":"2019","unstructured":"Garber C, Soung A, Vollmer LL, Kanmogne M, Last A, Brown J et al (2019) T cells promote microglia-mediated synaptic elimination and cognitive dysfunction during recovery from neuropathogenic flaviviruses. Nat Neurosci 22:1276\u20131288. https:\/\/doi.org\/10.1038\/s41593-019-0427-y","journal-title":"Nat Neurosci"},{"key":"2882_CR20","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1111\/ene.14139","volume":"27","author":"M Gastaldi","year":"2020","unstructured":"Gastaldi M, Mariotto S, Giannoccaro MP, Iorio R, Zoccarato M, Nosadini M et al (2020) Subgroup comparison according to clinical phenotype and serostatus in autoimmune encephalitis: a multicenter retrospective study. Eur J Neurol 27:633\u2013643. https:\/\/doi.org\/10.1111\/ene.14139","journal-title":"Eur J Neurol"},{"key":"2882_CR21","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1038\/s41398-020-00989-x","volume":"10","author":"LL Gibson","year":"2020","unstructured":"Gibson LL, McKeever A, Coutinho E, Finke C, Pollak TA (2020) Cognitive impact of neuronal antibodies: encephalitis and beyond. Transl Psychiatry 10:304. https:\/\/doi.org\/10.1038\/s41398-020-00989-x","journal-title":"Transl Psychiatry"},{"key":"2882_CR22","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/S1474-4422(15)00401-9","volume":"15","author":"F Graus","year":"2016","unstructured":"Graus F, Titulaer MJ, Balu R, Benseler S, Bien CG, Cellucci T et al (2016) A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol 15:391\u2013404. https:\/\/doi.org\/10.1016\/S1474-4422(15)00401-9","journal-title":"Lancet Neurol"},{"key":"2882_CR23","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/ana.26241","volume":"90","author":"J Heine","year":"2021","unstructured":"Heine J, Kopp UA, Klag J, Ploner CJ, Pruss H, Finke C (2021) Long-term cognitive outcome in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol 90:949\u2013961. https:\/\/doi.org\/10.1002\/ana.26241","journal-title":"Ann Neurol"},{"key":"2882_CR24","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1126\/science.aad8373","volume":"352","author":"S Hong","year":"2016","unstructured":"Hong S, Beja-Glasser VF, Nfonoyim BM, Frouin A, Li S, Ramakrishnan S et al (2016) Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science 352:712\u2013716. https:\/\/doi.org\/10.1126\/science.aad8373","journal-title":"Science"},{"key":"2882_CR25","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000000075","volume":"2","author":"P Kortvelyessy","year":"2015","unstructured":"Kortvelyessy P, Bauer J, Stoppel CM, Bruck W, Gerth I, Vielhaber S et al (2015) Complement-associated neuronal loss in a patient with CASPR2 antibody-associated encephalitis. Neurol Neuroimmunol Neuroinflamm 2:e75. https:\/\/doi.org\/10.1212\/NXI.0000000000000075","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2882_CR26","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1084\/jem.20122143","volume":"210","author":"M Kreutzfeldt","year":"2013","unstructured":"Kreutzfeldt M, Bergthaler A, Fernandez M, Bruck W, Steinbach K, Vorm M et al (2013) Neuroprotective intervention by interferon-gamma blockade prevents CD8+ T cell-mediated dendrite and synapse loss. J Exp Med 210:2087\u20132103. https:\/\/doi.org\/10.1084\/jem.20122143","journal-title":"J Exp Med"},{"key":"2882_CR27","doi-asserted-by":"publisher","first-page":"W90","DOI":"10.1093\/nar\/gkw377","volume":"44","author":"MV Kuleshov","year":"2016","unstructured":"Kuleshov MV, Jones MR, Rouillard AD, Fernandez NF, Duan Q, Wang Z et al (2016) Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucleic Acids Res 44:W90-97. https:\/\/doi.org\/10.1093\/nar\/gkw377","journal-title":"Nucleic Acids Res"},{"key":"2882_CR28","doi-asserted-by":"publisher","first-page":"3509","DOI":"10.1093\/brain\/awac166","volume":"145","author":"WJ Lee","year":"2022","unstructured":"Lee WJ, Lee HS, Kim DY, Lee HS, Moon J, Park KI et al (2022) Seronegative autoimmune encephalitis: clinical characteristics and factors associated with outcomes. Brain 145:3509\u20133521. https:\/\/doi.org\/10.1093\/brain\/awac166","journal-title":"Brain"},{"key":"2882_CR29","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","volume":"541","author":"SA Liddelow","year":"2017","unstructured":"Liddelow SA, Guttenplan KA, Clarke LE, Bennett FC, Bohlen CJ, Schirmer L et al (2017) Neurotoxic reactive astrocytes are induced by activated microglia. Nature 541:481\u2013487. https:\/\/doi.org\/10.1038\/nature21029","journal-title":"Nature"},{"key":"2882_CR30","doi-asserted-by":"publisher","first-page":"2066","DOI":"10.1093\/brain\/awy151","volume":"141","author":"J Machado-Santos","year":"2018","unstructured":"Machado-Santos J, Saji E, Troscher AR, Paunovic M, Liblau R, Gabriely G et al (2018) The compartmentalized inflammatory response in the multiple sclerosis brain is composed of tissue-resident CD8+ T lymphocytes and B cells. Brain 141:2066\u20132082. https:\/\/doi.org\/10.1093\/brain\/awy151","journal-title":"Brain"},{"key":"2882_CR31","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1016\/j.tim.2020.03.003","volume":"28","author":"ME Marcocci","year":"2020","unstructured":"Marcocci ME, Napoletani G, Protto V, Kolesova O, Piacentini R, Li Puma DD et al (2020) Herpes simplex virus-1 in the brain: the dark side of a sneaky infection. Trends Microbiol 28:808\u2013820. https:\/\/doi.org\/10.1016\/j.tim.2020.03.003","journal-title":"Trends Microbiol"},{"key":"2882_CR32","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1212\/WNL.0b013e318228c136","volume":"77","author":"E Martinez-Hernandez","year":"2011","unstructured":"Martinez-Hernandez E, Horvath J, Shiloh-Malawsky Y, Sangha N, Martinez-Lage M, Dalmau J (2011) Analysis of complement and plasma cells in the brain of patients with anti-NMDAR encephalitis. Neurology 77:589\u2013593. https:\/\/doi.org\/10.1212\/WNL.0b013e318228c136","journal-title":"Neurology"},{"key":"2882_CR33","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1146\/annurev-immunol-042617-053214","volume":"37","author":"D Masopust","year":"2019","unstructured":"Masopust D, Soerens AG (2019) Tissue-resident T cells and other resident leukocytes. Annu Rev Immunol 37:521\u2013546. https:\/\/doi.org\/10.1146\/annurev-immunol-042617-053214","journal-title":"Annu Rev Immunol"},{"key":"2882_CR34","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2022-329195","author":"S Matricardi","year":"2022","unstructured":"Matricardi S, Casciato S, Bozzetti S, Mariotto S, Stabile A, Freri E et al (2022) Epileptic phenotypes in autoimmune encephalitis: from acute symptomatic seizures to autoimmune-associated epilepsy. J Neurol Neurosurg Psychiatry. https:\/\/doi.org\/10.1136\/jnnp-2022-329195","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"2882_CR35","doi-asserted-by":"publisher","first-page":"2709","DOI":"10.1093\/brain\/awab153","volume":"144","author":"S Muniz-Castrillo","year":"2021","unstructured":"Muniz-Castrillo S, Hedou JJ, Ambati A, Jones D, Vogrig A, Pinto AL et al (2021) Distinctive clinical presentation and pathogenic specificities of anti-AK5 encephalitis. Brain 144:2709\u20132721. https:\/\/doi.org\/10.1093\/brain\/awab153","journal-title":"Brain"},{"key":"2882_CR36","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1007\/s12311-021-01363-3","volume":"21","author":"S Muniz-Castrillo","year":"2022","unstructured":"Muniz-Castrillo S, Vogrig A, Ciano-Petersen NL, Villagran-Garcia M, Joubert B, Honnorat J (2022) Novelties in autoimmune and paraneoplastic cerebellar ataxias: twenty years of progresses. Cerebellum 21:573\u2013591. https:\/\/doi.org\/10.1007\/s12311-021-01363-3","journal-title":"Cerebellum"},{"key":"2882_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01818-w","author":"M Pereira-Iglesias","year":"2024","unstructured":"Pereira-Iglesias M, Maldonado-Teixido J, Melero A, Piriz J, Galea E, Ransohoff RM et al (2024) Microglia as hunters or gatherers of brain synapses. Nat Neurosci. https:\/\/doi.org\/10.1038\/s41593-024-01818-w","journal-title":"Nat Neurosci"},{"key":"2882_CR38","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1016\/j.cell.2019.08.053","volume":"179","author":"M Prinz","year":"2019","unstructured":"Prinz M, Jung S, Priller J (2019) Microglia biology: one century of evolving concepts. Cell 179:292\u2013311. https:\/\/doi.org\/10.1016\/j.cell.2019.08.053","journal-title":"Cell"},{"key":"2882_CR39","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1038\/s41577-021-00543-w","volume":"21","author":"H Pruss","year":"2021","unstructured":"Pruss H (2021) Autoantibodies in neurological disease. Nat Rev Immunol 21:798\u2013813. https:\/\/doi.org\/10.1038\/s41577-021-00543-w","journal-title":"Nat Rev Immunol"},{"key":"2882_CR40","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1093\/brain\/awaa104","volume":"143","author":"M Ramberger","year":"2020","unstructured":"Ramberger M, Berretta A, Tan JMM, Sun B, Michael S, Yeo T et al (2020) Distinctive binding properties of human monoclonal LGI1 autoantibodies determine pathogenic mechanisms. Brain 143:1731\u20131745. https:\/\/doi.org\/10.1093\/brain\/awaa104","journal-title":"Brain"},{"key":"2882_CR41","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/j.neuron.2012.03.026","volume":"74","author":"DP Schafer","year":"2012","unstructured":"Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R et al (2012) Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74:691\u2013705. https:\/\/doi.org\/10.1016\/j.neuron.2012.03.026","journal-title":"Neuron"},{"key":"2882_CR42","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1126\/science.1254536","volume":"346","author":"JM Schenkel","year":"2014","unstructured":"Schenkel JM, Fraser KA, Beura LK, Pauken KE, Vezys V, Masopust D (2014) T cell memory. Resident memory CD8 T cells trigger protective innate and adaptive immune responses. Science 346:98\u2013101. https:\/\/doi.org\/10.1126\/science.1254536","journal-title":"Science"},{"key":"2882_CR43","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/j.neuron.2024.12.006","volume":"113","author":"Y Segal","year":"2025","unstructured":"Segal Y, Soltys J, Clarkson BDS, Howe CL, Irani SR, Pittock SJ (2025) Toward curing neurological autoimmune disorders: biomarkers, immunological mechanisms, and therapeutic targets. Neuron 113:345\u2013379. https:\/\/doi.org\/10.1016\/j.neuron.2024.12.006","journal-title":"Neuron"},{"key":"2882_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.107843","volume":"31","author":"K Srinivasan","year":"2020","unstructured":"Srinivasan K, Friedman BA, Etxeberria A, Huntley MA, van der Brug MP, Foreman O et al (2020) Alzheimer\u2019s patient microglia exhibit enhanced aging and unique transcriptional activation. Cell Rep 31:107843. https:\/\/doi.org\/10.1016\/j.celrep.2020.107843","journal-title":"Cell Rep"},{"key":"2882_CR45","doi-asserted-by":"publisher","first-page":"1571","DOI":"10.1084\/jem.20151916","volume":"213","author":"K Steinbach","year":"2016","unstructured":"Steinbach K, Vincenti I, Kreutzfeldt M, Page N, Muschaweckh A, Wagner I et al (2016) Brain-resident memory T cells represent an autonomous cytotoxic barrier to viral infection. J Exp Med 213:1571\u20131587. https:\/\/doi.org\/10.1084\/jem.20151916","journal-title":"J Exp Med"},{"key":"2882_CR46","doi-asserted-by":"publisher","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","volume":"131","author":"B Stevens","year":"2007","unstructured":"Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N et al (2007) The classical complement cascade mediates CNS synapse elimination. Cell 131:1164\u20131178. https:\/\/doi.org\/10.1016\/j.cell.2007.10.036","journal-title":"Cell"},{"key":"2882_CR47","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/s41582-020-0381-z","volume":"16","author":"B Sun","year":"2020","unstructured":"Sun B, Ramberger M, O\u2019Connor KC, Bashford-Rogers RJM, Irani SR (2020) The B cell immunobiology that underlies CNS autoantibody-mediated diseases. Nat Rev Neurol 16:481\u2013492. https:\/\/doi.org\/10.1038\/s41582-020-0381-z","journal-title":"Nat Rev Neurol"},{"key":"2882_CR48","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1093\/brain\/awx323","volume":"141","author":"J Thompson","year":"2018","unstructured":"Thompson J, Bi M, Murchison AG, Makuch M, Bien CG, Chu K et al (2018) The importance of early immunotherapy in patients with faciobrachial dystonic seizures. Brain 141:348\u2013356. https:\/\/doi.org\/10.1093\/brain\/awx323","journal-title":"Brain"},{"key":"2882_CR49","doi-asserted-by":"publisher","first-page":"1436","DOI":"10.1093\/brain\/awac404","volume":"146","author":"AR Troscher","year":"2023","unstructured":"Troscher AR, Mair KM, Verdu de Juan L, Kock U, Steinmaurer A, Baier H et al (2023) Temporal lobe epilepsy with GAD antibodies: neurons killed by T cells not by complement membrane attack complex. Brain 146:1436\u20131452. https:\/\/doi.org\/10.1093\/brain\/awac404","journal-title":"Brain"},{"key":"2882_CR50","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1007\/s00401-009-0582-4","volume":"118","author":"E Tuzun","year":"2009","unstructured":"Tuzun E, Zhou L, Baehring JM, Bannykh S, Rosenfeld MR, Dalmau J (2009) Evidence for antibody-mediated pathogenesis in anti-NMDAR encephalitis associated with ovarian teratoma. Acta Neuropathol 118:737\u2013743. https:\/\/doi.org\/10.1007\/s00401-009-0582-4","journal-title":"Acta Neuropathol"},{"key":"2882_CR51","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1136\/practneurol-2020-002567","volume":"21","author":"CE Uy","year":"2021","unstructured":"Uy CE, Binks S, Irani SR (2021) Autoimmune encephalitis: clinical spectrum and management. Pract Neurol 21:412\u2013423. https:\/\/doi.org\/10.1136\/practneurol-2020-002567","journal-title":"Pract Neurol"},{"key":"2882_CR52","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1212\/WNL.0000000000002917","volume":"87","author":"A van Sonderen","year":"2016","unstructured":"van Sonderen A, Arino H, Petit-Pedrol M, Leypoldt F, Kortvelyessy P, Wandinger KP et al (2016) The clinical spectrum of Caspr2 antibody-associated disease. Neurology 87:521\u2013528. https:\/\/doi.org\/10.1212\/WNL.0000000000002917","journal-title":"Neurology"},{"key":"2882_CR53","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1038\/nature18283","volume":"534","author":"MJ Vasek","year":"2016","unstructured":"Vasek MJ, Garber C, Dorsey D, Durrant DM, Bollman B, Soung A et al (2016) A complement-microglial axis drives synapse loss during virus-induced memory impairment. Nature 534:538\u2013543. https:\/\/doi.org\/10.1038\/nature18283","journal-title":"Nature"},{"key":"2882_CR54","doi-asserted-by":"publisher","first-page":"eabl6058","DOI":"10.1126\/scitranslmed.abl6058","volume":"14","author":"I Vincenti","year":"2022","unstructured":"Vincenti I, Page N, Steinbach K, Yermanos A, Lemeille S, Nunez N et al (2022) Tissue-resident memory CD8(+) T cells cooperate with CD4(+) T cells to drive compartmentalized immunopathology in the CNS. Sci Transl Med 14:eabl6058. https:\/\/doi.org\/10.1126\/scitranslmed.abl6058","journal-title":"Sci Transl Med"},{"key":"2882_CR55","doi-asserted-by":"publisher","first-page":"17872","DOI":"10.1073\/pnas.1010201107","volume":"107","author":"LM Wakim","year":"2010","unstructured":"Wakim LM, Woodward-Davis A, Bevan MJ (2010) Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence. Proc Natl Acad Sci U S A 107:17872\u201317879. https:\/\/doi.org\/10.1073\/pnas.1010201107","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2882_CR56","doi-asserted-by":"publisher","first-page":"eadn9980","DOI":"10.1126\/scitranslmed.adn9980","volume":"17","author":"Q Wang","year":"2025","unstructured":"Wang Q, Huang T, Zheng Z, Su Y, Wu Z, Zeng C et al (2025) Oligodendroglial precursor cells modulate immune response and early demyelination in a murine model of multiple sclerosis. Sci Transl Med 17:eadn9980. https:\/\/doi.org\/10.1126\/scitranslmed.adn9980","journal-title":"Sci Transl Med"},{"issue":"167\u2013182","key":"2882_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.12.004","volume":"52","author":"S Werneburg","year":"2020","unstructured":"Werneburg S, Jung J, Kunjamma RB, Ha SK, Luciano NJ, Willis CM et al (2020) Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease. Immunity 52(167\u2013182):e167. https:\/\/doi.org\/10.1016\/j.immuni.2019.12.004","journal-title":"Immunity"},{"key":"2882_CR58","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.cell.2022.12.032","volume":"186","author":"DM Wilson 3rd","year":"2023","unstructured":"Wilson DM 3rd, Cookson MR, Van Den Bosch L, Zetterberg H, Holtzman DM, Dewachter I (2023) Hallmarks of neurodegenerative diseases. Cell 186:693\u2013714. https:\/\/doi.org\/10.1016\/j.cell.2022.12.032","journal-title":"Cell"},{"key":"2882_CR59","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200006","author":"M Winklehner","year":"2022","unstructured":"Winklehner M, Bauer J, Endmayr V, Schwaiger C, Ricken G, Motomura M et al (2022) Paraneoplastic cerebellar degeneration with P\/Q-VGCC vs Yo autoantibodies. Neurol Neuroimmunol Neuroinflamm. https:\/\/doi.org\/10.1212\/NXI.0000000000200006","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"key":"2882_CR60","doi-asserted-by":"publisher","DOI":"10.1212\/NXI.0000000000200298","volume":"11","author":"M Winklehner","year":"2024","unstructured":"Winklehner M, Wickel J, Gelpi E, Bramer D, Rauschenberger V, Gunther A et al (2024) Progressive encephalomyelitis with rigidity and myoclonus with glycine receptor and GAD65 antibodies: case report and potential mechanisms. Neurol Neuroimmunol Neuroinflamm 11:e200298. https:\/\/doi.org\/10.1212\/NXI.0000000000200298","journal-title":"Neurol Neuroimmunol Neuroinflamm"},{"issue":"1333\u20131349","key":"2882_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2021.03.006","volume":"109","author":"M Yasuda","year":"2021","unstructured":"Yasuda M, Nagappan-Chettiar S, Johnson-Venkatesh EM, Umemori H (2021) An activity-dependent determinant of synapse elimination in the mammalian brain. Neuron 109(1333\u20131349):e1336. https:\/\/doi.org\/10.1016\/j.neuron.2021.03.006","journal-title":"Neuron"},{"key":"2882_CR62","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.127001","author":"L Yshii","year":"2019","unstructured":"Yshii L, Pignolet B, Maure E, Pierau M, Brunner-Weinzierl M, Hartley O et al (2019) IFN-gamma is a therapeutic target in paraneoplastic cerebellar degeneration. JCI Insight. https:\/\/doi.org\/10.1172\/jci.insight.127001","journal-title":"JCI Insight"},{"key":"2882_CR63","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1002\/ana.26223","volume":"90","author":"T Zrzavy","year":"2021","unstructured":"Zrzavy T, Endmayr V, Bauer J, Macher S, Mossaheb N, Schwaiger C et al (2021) Neuropathological variability within a spectrum of NMDAR-encephalitis. Ann Neurol 90:725\u2013737. https:\/\/doi.org\/10.1002\/ana.26223","journal-title":"Ann Neurol"}],"container-title":["Acta Neuropathologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02882-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00401-025-02882-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00401-025-02882-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T15:02:17Z","timestamp":1745593337000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00401-025-02882-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,25]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["2882"],"URL":"https:\/\/doi.org\/10.1007\/s00401-025-02882-7","relation":{},"ISSN":["1432-0533"],"issn-type":[{"value":"1432-0533","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,25]]},"assertion":[{"value":"30 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 April 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"35"}}