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@ARTICLE{DiLiberto:278073,
author = {Di Liberto, Giovanni and Egervari, Kristof and Vogrig,
Alberto and Spatola, Marianna and Piccinno, Margot and
Vincenti, Ilena and Wagner, Ingrid and Kreutzfeldt, Mario
and Endmayr, Verena and Ostertag, Karoline and Rahimi,
Jasmin and Vicino, Alex and Pröbstel, Anne-Katrin and
Meyronet, David and Frank, Stephan and Prinz, Marco and
Hewer, Ekkehard and Brouland, Jean-Philippe and de Leval,
Laurence and Parkkinen, Laura and Draganski, Bogdan and
Desestret, Virginie and Dubey, Divyanshu and Pittock, Sean J
and Roemer, Shanu F and Dickson, Dennis W and Höftberger,
Romana and Irani, Sarosh R and Honnorat, Jérôme and Du
Pasquier, Renaud and Merkler, Doron},
title = {{N}euronal p{STAT}1 hallmarks synaptic pathology in
autoimmune encephalitis against intracellular antigens.},
journal = {Acta neuropathologica},
volume = {149},
number = {1},
issn = {0001-6322},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2025-00564},
pages = {35},
year = {2025},
abstract = {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.},
keywords = {Humans / Encephalitis: pathology / Encephalitis: immunology
/ Encephalitis: metabolism / Female / Male / Middle Aged /
Neurons: pathology / Neurons: immunology / Neurons:
metabolism / Hashimoto Disease: pathology / Hashimoto
Disease: immunology / Adult / STAT1 Transcription Factor:
metabolism / Synapses: pathology / Synapses: immunology /
Synapses: metabolism / Aged / Autoantigens: immunology /
Brain: pathology / Brain: immunology / CD8-Positive
T-Lymphocytes: immunology / CD8-Positive T-Lymphocytes:
pathology / Young Adult / Neurodegeneration (Other) /
Neuroinflammation (Other) / Phagocytes (Other) / Resident
memory T cells (Other) / Synapses (Other) / STAT1
Transcription Factor (NLM Chemicals) / Autoantigens (NLM
Chemicals)},
cin = {AG Pröbstel},
ddc = {610},
cid = {I:(DE-2719)1013045},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40278930},
pmc = {pmc:PMC12031792},
doi = {10.1007/s00401-025-02882-7},
url = {https://pub.dzne.de/record/278073},
}