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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Vydané v:	Acta neuropathologica Ročník 149; číslo 1; s. 35
Hlavní autori:	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
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Berlin/Heidelberg Springer Berlin Heidelberg 25.04.2025 Springer Nature B.V
Predmet:	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
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Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	1432-0533 0001-6322 1432-0533
DOI:	10.1007/s00401-025-02882-7