%0 Journal Article
%A Di Liberto, Giovanni
%A Egervari, Kristof
%A Vogrig, Alberto
%A Spatola, Marianna
%A Piccinno, Margot
%A Vincenti, Ilena
%A Wagner, Ingrid
%A Kreutzfeldt, Mario
%A Endmayr, Verena
%A Ostertag, Karoline
%A Rahimi, Jasmin
%A Vicino, Alex
%A Pröbstel, Anne-Katrin
%A Meyronet, David
%A Frank, Stephan
%A Prinz, Marco
%A Hewer, Ekkehard
%A Brouland, Jean-Philippe
%A de Leval, Laurence
%A Parkkinen, Laura
%A Draganski, Bogdan
%A Desestret, Virginie
%A Dubey, Divyanshu
%A Pittock, Sean J
%A Roemer, Shanu F
%A Dickson, Dennis W
%A Höftberger, Romana
%A Irani, Sarosh R
%A Honnorat, Jérôme
%A Du Pasquier, Renaud
%A Merkler, Doron
%T Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens.
%J Acta neuropathologica
%V 149
%N 1
%@ 0001-6322
%C Heidelberg
%I Springer
%M DZNE-2025-00564
%P 35
%D 2025
%X 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 = 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.
%K Humans
%K Encephalitis: pathology
%K Encephalitis: immunology
%K Encephalitis: metabolism
%K Female
%K Male
%K Middle Aged
%K Neurons: pathology
%K Neurons: immunology
%K Neurons: metabolism
%K Hashimoto Disease: pathology
%K Hashimoto Disease: immunology
%K Adult
%K STAT1 Transcription Factor: metabolism
%K Synapses: pathology
%K Synapses: immunology
%K Synapses: metabolism
%K Aged
%K Autoantigens: immunology
%K Brain: pathology
%K Brain: immunology
%K CD8-Positive T-Lymphocytes: immunology
%K CD8-Positive T-Lymphocytes: pathology
%K Young Adult
%K Neurodegeneration (Other)
%K Neuroinflammation (Other)
%K Phagocytes (Other)
%K Resident memory T cells (Other)
%K Synapses (Other)
%K STAT1 Transcription Factor (NLM Chemicals)
%K Autoantigens (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40278930
%2 pmc:PMC12031792
%R 10.1007/s00401-025-02882-7
%U https://pub.dzne.de/record/278073