Di Liberto, GiovanniGiovanniDi LibertoEgervari, KristofKristofEgervariVogrig, AlbertoAlbertoVogrigSpatola, MariannaMariannaSpatolaPiccinno, MargotMargotPiccinnoVincenti, IlenaIlenaVincentiWagner, IngridIngridWagnerKreutzfeldt, MarioMarioKreutzfeldtEndmayr, VerenaVerenaEndmayrOstertag, KarolineKarolineOstertagRahimi, JasminJasminRahimiVicino, AlexAlexVicinoPröbstel, Anne-KatrinAnne-KatrinPröbstelMeyronet, DavidDavidMeyronetFrank, StephanStephanFrankPrinz, MarcoMarcoPrinzHewer, EkkehardEkkehardHewer0000-0002-9128-0364Brouland, Jean-PhilippeJean-PhilippeBroulandde Leval, LaurenceLaurencede LevalParkkinen, LauraLauraParkkinenDraganski, BogdanBogdanDraganskiDesestret, VirginieVirginieDesestretDubey, DivyanshuDivyanshuDubeyPittock, Sean JSean JPittockRoemer, Shanu FShanu FRoemerDickson, Dennis WDennis WDicksonHöftberger, RomanaRomanaHöftbergerIrani, Sarosh RSarosh RIraniHonnorat, JérômeJérômeHonnoratDu Pasquier, RenaudRenaudDu PasquierMerkler, DoronDoronMerkler2025-05-202025-05-202025-04-25https://boris-portal.unibe.ch/handle/20.500.12422/210216Autoimmune 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 = 8) and IC-AE (n = 12) 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 + T cells and neurodegenerative GPNMB + phagocytes 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.enNeurodegenerationNeuroinflammationPhagocytesResident memory T cellsSynapses600 - Technology::610 - Medicine & healtharticle10.48620/881344027893010.1007/s00401-025-02882-7