Peripheral T-cell subset activation in NMDAR encephalitis: Insights into pathogenesis and biomarker potential for disease monitoring.
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BACKGROUND: N-methyl-d-aspartate receptor encephalitis (NMDAR-E) is a severe autoimmune disorder characterized by neuropsychiatric symptoms and immune dysregulation ,involves T-cell dysregulation, but specific T-cell subset roles remain unclear. This study analyzed peripheral blood T-cell subsets as biomarkers for monitoring and severity prediction. METHODS: Peripheral blood samples from 32 NMDAR-E patients, 31 antibody-mediated encephalitis, 26 viral encephalitis patients, and 23 healthy controls were analyzed using flow cytometry. Key markers of T-cell activation and co-stimulation were assessed. Clinical outcomes were correlated with immune profiles to develop a predictive model. RESULTS: NMDAR-E patients showed elevated CD4+ T-cell activation, with increased CD28, CD38, and HLA-DR expression versus controls, indicating immune hyperactivation with compensatory regulation. The T-cell-based model predicted severe cases with high accuracy (AUC = 0.91). CONCLUSION: CD4+ T-cell activation is central to NMDAR-E pathogenesis, highlighting diagnostic/therapeutic potential. Future studies must validate the model in larger cohorts and address peripheral blood analysis limitations.