Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens

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...

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Bibliographic Details
Published in:Acta neuropathologica Vol. 149; no. 1; p. 35
Main Authors: Di Liberto, Giovanni, Egervari, Kristof, Vogrig, Alberto, Spatola, Marianna, Piccinno, Margot, Vincenti, Ilena, Wagner, Ingrid, Kreutzfeldt, Mario, Endmayr, Verena, Ostertag, Karoline, Rahimi, Jasmin, Vicino, Alex, Pröbstel, Anne-Katrin, Meyronet, David, Frank, Stephan, Prinz, Marco, Hewer, Ekkehard, Brouland, Jean-Philippe, de Leval, Laurence, Parkkinen, Laura, Draganski, Bogdan, Desestret, Virginie, Dubey, Divyanshu, Pittock, Sean J., Roemer, Shanu F., Dickson, Dennis W., Höftberger, Romana, Irani, Sarosh R., Honnorat, Jérôme, Du Pasquier, Renaud, Merkler, Doron
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 25.04.2025
Springer Nature B.V
Subjects:
Adult
Aged
Antibodies
Antigens
Autoantigens
Autoantigens - immunology
Autoimmune diseases
Biomarkers
Brain - immunology
Brain - pathology
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - pathology
Central nervous system
Complement component C3
Disease
Encephalitis
Encephalitis - immunology
Encephalitis - metabolism
Encephalitis - pathology
Female
Females
Genotype & phenotype
Hashimoto Disease - immunology
Hashimoto Disease - pathology
Humans
Immunological memory
Intracellular
Lymphocytes
Lymphocytes T
Male
Males
Medical prognosis
Medicine
Medicine & Public Health
Memory
Memory cells
Middle Aged
Nervous system
Neurodegeneration
Neurons - immunology
Neurons - metabolism
Neurons - pathology
Neurosciences
Original Paper
Pathogenesis
Pathology
Phagocytes
Proteins
STAT1 Transcription Factor - metabolism
Synapses - immunology
Synapses - metabolism
Synapses - pathology
Young Adult
Phagocytes
Neuroinflammation
Resident memory T cells
Neurodegeneration
Synapses
ISSN:1432-0533, 0001-6322, 1432-0533
Online Access:Get full text
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Summary: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.
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ISSN:1432-0533
0001-6322
1432-0533
DOI:10.1007/s00401-025-02882-7