Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Acta Neuropathologica
Authors: Giovanni Di Liberto, Kristof Egervari, Alberto Vogrig, Marianna Spatola, Margot Piccinno, Ilena Vincenti, Ingrid Wagner, Mario Kreutzfeldt, Verena Endmayr, Karoline Ostertag, Jasmin Rahimi, Alex Vicino, Anne-Katrin Pröbstel, David Meyronet, Stephan Frank, Marco Prinz, Ekkehard Hewer, Jean-Philippe Brouland, Laurence de Leval, Laura Parkkinen, Bogdan Draganski, Virginie Desestret, Divyanshu Dubey, Sean J. Pittock, Shanu F. Roemer, Dennis W. Dickson, Romana Höftberger, Sarosh R. Irani, Jérôme Honnorat, Renaud Du Pasquier, Doron Merkler
Institutions: University of Geneva, Centre Hospitalier Universitaire Vaudois, University of Lausanne, University Hospital of Geneva, University of Udine, Azienda sanitaria universitaria Friuli Centrale, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, CaixaResearch Institute, Universitat de Barcelona, Medical University of Vienna, Klinik Hietzing, University of Bonn, University of Basel, University Hospital Bonn, German Center for Neurodegenerative Diseases, University Hospital of Basel, Lyon 1 Université, Centre National de la Recherche Scientifique, Inserm, Université de Lyon, Hospices Civils de Lyon, Centre de Recherche en Cancérologie de Lyon, University of Freiburg, University of Oxford, University of Bern, University Hospital of Bern, Mécanismes en sciences intégratives du vivant, Mayo Clinic, Mayo Clinic in Florida, John Radcliffe Hospital
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,990
Awards: Autologous human induced pluripotent stem cells-derived neurons, astrocytes and oligodendrocytes as T cells targets in multiple sclerosis, Neuromodulation-induced plasticity of hippocampal networks – diagnostic and prognostic value for mood, cognitive and motor outcome in depression, MicroBe - Towards harnessing Microbiota - B cell interaction for immune modulation in neuroinflammation, DeeBdiviN – Deciphering B cell diversity in Neuroinflammation, Regulators of long-term dyshomeostasis in chronic neuroinflammation, I-See - Improving intracortical visual prostheses using complex coding and spontaneous activation states, Connecting properties of the micro- and macrovasculature from multimodal imaging through genetics and deep learning to better understand vascular pathomechanisms and predict disease risk, Brain Age Prediction – Diagnostic method or reconceptualizing age, G7391270233, Biomarkers in autoimmune EncephaliTis and Paraneoplastic neurological SYndromes, G8690818240, G880118091
OpenAlex ID: W4409785338