Journal Article

DZNE-2025-00564

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens.

Di Liberto, G. ; Egervari, K. ; Vogrig, A. ; Spatola, M. ; Piccinno, M. ; Vincenti, I. ; Wagner, I. ; Kreutzfeldt, M. ; Endmayr, V. ; Ostertag, K. ; Rahimi, J. ; Vicino, A. ; Pröbstel, A.-K.DZNE* ; Meyronet, D. ; Frank, S. ; Prinz, M. ; Hewer, E. ; Brouland, J.-P. ; de Leval, L. ; Parkkinen, L. ; Draganski, B. ; Desestret, V. ; Dubey, D. ; Pittock, S. J. ; Roemer, S. F. ; Dickson, D. W. ; Höftberger, R. ; Irani, S. R. ; Honnorat, J. ; Du Pasquier, R. ; Merkler, D.

2025
Springer Heidelberg

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Please use a persistent id in citations: doi:10.1007/s00401-025-02882-7

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.

Keyword(s): Humans (MeSH) ; Encephalitis: pathology (MeSH) ; Encephalitis: immunology (MeSH) ; Encephalitis: metabolism (MeSH) ; Female (MeSH) ; Male (MeSH) ; Middle Aged (MeSH) ; Neurons: pathology (MeSH) ; Neurons: immunology (MeSH) ; Neurons: metabolism (MeSH) ; Hashimoto Disease: pathology (MeSH) ; Hashimoto Disease: immunology (MeSH) ; Adult (MeSH) ; STAT1 Transcription Factor: metabolism (MeSH) ; Synapses: pathology (MeSH) ; Synapses: immunology (MeSH) ; Synapses: metabolism (MeSH) ; Aged (MeSH) ; Autoantigens: immunology (MeSH) ; Brain: pathology (MeSH) ; Brain: immunology (MeSH) ; CD8-Positive T-Lymphocytes: immunology (MeSH) ; CD8-Positive T-Lymphocytes: pathology (MeSH) ; Young Adult (MeSH) ; Neurodegeneration ; Neuroinflammation ; Phagocytes ; Resident memory T cells ; Synapses ; STAT1 Transcription Factor ; Autoantigens

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Contributing Institute(s):

1. Clinical Neurology and Neuroimmunology (AG Pröbstel)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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