Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens
Copyright policy )Neuronal pSTAT1 hallmarks synaptic pathology in autoimmune encephalitis against intracellular antigens
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.
- University Hospital of Basel Switzerland
- Medical University of Vienna Austria
- German Center for Neurodegenerative Diseases Germany
- University of Bonn Germany
- University of Lyon System France
Male, Synapses: immunology, CD8-Positive T-Lymphocytes, Autoantigens, Neurons: immunology, Neurons / pathology, Neuroinflammation, Hashimoto Disease: immunology, Brain: immunology, Encephalitis / metabolism, 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; Neuroinflammation; Phagocytes; Resident memory T cells; Synapses, info:eu-repo/classification/ddc/610, Neurons, Phagocytes, Neurons / metabolism, Brain / immunology, Brain / pathology, Autoantigens: immunology, Brain, CD8-Positive T-Lymphocytes: pathology, Synapses: pathology, Middle Aged, CD8-Positive T-Lymphocytes / immunology, STAT1 Transcription Factor, Hashimoto Disease / pathology, STAT1 Transcription Factor / metabolism, Encephalitis, Encephalitis: metabolism, Female, Adult, Neurons: metabolism, Encephalitis / immunology, Resident memory T cells, Hashimoto Disease, 616.07, Autoantigens / immunology, Hashimoto Disease / immunology, Young Adult, Synapses: metabolism, STAT1 Transcription Factor: metabolism, Synapses / immunology, Humans, Encephalitis: immunology, Neurodegeneration, Encephalitis: pathology, Aged, Hashimoto Disease: pathology, Original Paper, Synapses / pathology, CD8-Positive T-Lymphocytes: immunology, Neurodegeneration; Neuroinflammation; Phagocytes; Resident memory T cells; Synapses, Neurons / immunology, Synapses / metabolism, Encephalitis / pathology, Brain: pathology, Neurons: pathology, CD8-Positive T-Lymphocytes / pathology, Synapses
Male, Synapses: immunology, CD8-Positive T-Lymphocytes, Autoantigens, Neurons: immunology, Neurons / pathology, Neuroinflammation, Hashimoto Disease: immunology, Brain: immunology, Encephalitis / metabolism, 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; Neuroinflammation; Phagocytes; Resident memory T cells; Synapses, info:eu-repo/classification/ddc/610, Neurons, Phagocytes, Neurons / metabolism, Brain / immunology, Brain / pathology, Autoantigens: immunology, Brain, CD8-Positive T-Lymphocytes: pathology, Synapses: pathology, Middle Aged, CD8-Positive T-Lymphocytes / immunology, STAT1 Transcription Factor, Hashimoto Disease / pathology, STAT1 Transcription Factor / metabolism, Encephalitis, Encephalitis: metabolism, Female, Adult, Neurons: metabolism, Encephalitis / immunology, Resident memory T cells, Hashimoto Disease, 616.07, Autoantigens / immunology, Hashimoto Disease / immunology, Young Adult, Synapses: metabolism, STAT1 Transcription Factor: metabolism, Synapses / immunology, Humans, Encephalitis: immunology, Neurodegeneration, Encephalitis: pathology, Aged, Hashimoto Disease: pathology, Original Paper, Synapses / pathology, CD8-Positive T-Lymphocytes: immunology, Neurodegeneration; Neuroinflammation; Phagocytes; Resident memory T cells; Synapses, Neurons / immunology, Synapses / metabolism, Encephalitis / pathology, Brain: pathology, Neurons: pathology, CD8-Positive T-Lymphocytes / pathology, Synapses
selected citations These citations are derived from selected sources.This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).7 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!