TY  - JOUR
AU  - Di Liberto, Giovanni
AU  - Egervari, Kristof
AU  - Vogrig, Alberto
AU  - Spatola, Marianna
AU  - Piccinno, Margot
AU  - Vincenti, Ilena
AU  - Wagner, Ingrid
AU  - Kreutzfeldt, Mario
AU  - Endmayr, Verena
AU  - Ostertag, Karoline
AU  - Rahimi, Jasmin
AU  - Vicino, Alex
AU  - Pröbstel, Anne-Katrin
AU  - Meyronet, David
AU  - Frank, Stephan
AU  - Prinz, Marco
AU  - Hewer, Ekkehard
AU  - Brouland, Jean-Philippe
AU  - de Leval, Laurence
AU  - Parkkinen, Laura
AU  - Draganski, Bogdan
AU  - Desestret, Virginie
AU  - Dubey, Divyanshu
AU  - Pittock, Sean J
AU  - Roemer, Shanu F
AU  - Dickson, Dennis W
AU  - Höftberger, Romana
AU  - Irani, Sarosh R
AU  - Honnorat, Jérôme
AU  - Du Pasquier, Renaud
AU  - Merkler, Doron
TI  - Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens.
JO  - Acta neuropathologica
VL  - 149
IS  - 1
SN  - 0001-6322
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2025-00564
SP  - 35
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Encephalitis: pathology
KW  - Encephalitis: immunology
KW  - Encephalitis: metabolism
KW  - Female
KW  - Male
KW  - Middle Aged
KW  - Neurons: pathology
KW  - Neurons: immunology
KW  - Neurons: metabolism
KW  - Hashimoto Disease: pathology
KW  - Hashimoto Disease: immunology
KW  - Adult
KW  - STAT1 Transcription Factor: metabolism
KW  - Synapses: pathology
KW  - Synapses: immunology
KW  - Synapses: metabolism
KW  - Aged
KW  - Autoantigens: immunology
KW  - Brain: pathology
KW  - Brain: immunology
KW  - CD8-Positive T-Lymphocytes: immunology
KW  - CD8-Positive T-Lymphocytes: pathology
KW  - Young Adult
KW  - Neurodegeneration (Other)
KW  - Neuroinflammation (Other)
KW  - Phagocytes (Other)
KW  - Resident memory T cells (Other)
KW  - Synapses (Other)
KW  - STAT1 Transcription Factor (NLM Chemicals)
KW  - Autoantigens (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40278930
C2  - pmc:PMC12031792
DO  - DOI:10.1007/s00401-025-02882-7
UR  - https://pub.dzne.de/record/278073
ER  -