A multi-omics analysis of CSF reveals the differential immunopathology molecular mechanisms underlying viral encephalitis and autoimmune encephalitis

Background: This study explores viral encephalitis (VE) and autoimmune encephalitis (AE), similar in symptoms but requiring distinct treatments. Early diagnosis is crucial for effective intervention. The research utilizes early cerebrospinal fluid (CSF) analysis, employing transcriptomics, proteomics, and metabolomics to understand the immunological aspects of VE and AE. Methods: Participants from the IMPROVE clinical trial (ClinicalTrial.gov, NCT04946682, July 1, 2021) between April 2018 and November 2022 were included. CSF samples at disease onset were analyzed for VE and AE immunological profiles. Results: CSF analysis from 34 VE patients, 29 AE patients, and 6 controls unveiled shared and distinct immune mechanisms. Compared to controls, VE and AE patients showed reduced neuronal transporter functions and increased T and B cell activation. VE exhibited heightened interferon responses, complement pathways, and CD8 ⁺ T cell functions. AE displayed unique modulations in CD4 ⁺ T cell and Treg cell activities, potentially reducing autoimmune responses. Both conditions induced damage to critical brain areas. Conclusion: The study identified immunological differences and similarities, emphasizing specific CSF molecular changes for differential diagnosis. Findings highlighted complex immune interactions, with both diseases involving suppressed neuronal functions and heightened T and B cell activities. VE featured distinct interferon and CD8 ⁺ T cell activations, while AE showed specialized CD4 ⁺ T and Treg cell modulations. Immune balance played a crucial role in encephalitis pathogenesis. Further studies are crucial to validate biomarkers for accurate diagnosis, paving the way for targeted therapies and improved management of these neurological disorders.