Abstract
OBJECTIVE: To investigate mitochondrial functional alterations in T lymphocytes of patients with anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR encephalitis, NMDAR-E) and their association with immune exhaustion. METHODS: Twenty-five patients with NMDAR-E diagnosed in the Department of Neurology, West China Hospital, Sichuan University, between January and March 2025 (14 mild cases and 11 severe cases) and 16 healthy controls were enrolled. Flow cytometry was performed to characterize immune-cell distributions in paired peripheral blood and cerebrospinal fluid (CSF), and to evaluate the percentage of cells with low mitochondrial membrane potential (MMP-Low%), mitochondrial mass (MM), and PD-1 expression. RESULTS: In severe patients, the proportions of CD3(+) and CD4(+) T cells in CSF, the MMP-Low% of CD3(+), CD4(+), and CD8(+) T cells (P < 0.01), and the MM of CD3(+) (P < 0.01) and CD8(+) T cells (P < 0.05) were all significantly higher than those in matched peripheral blood. Compared with healthy controls, the MMP-Low% of naïve and central memory CD4(+) and CD8(+) T-cell subsets in peripheral blood was significantly decreased (P < 0.05), whereas the proportion of PD-1-positive cells was significantly increased in CD4(+)naïve and central memory T-cell subsets (P < 0.01). CONCLUSION: CSF T cells in patients with anti-NMDAR encephalitis display a state of dysfunctional mitochondrial accumulation, suggesting a possible dysregulation of mitochondrial mass homeostasis under the central inflammatory milieu. Mitochondrial features of peripheral T cells indicate the presence of systemic immune exhaustion. The MMP-Low% of CSF CD8(+) T cells and the peripheral blood lymphocyte percentage may serve as potential immunometabolic biomarkers for distinguishing disease severity in NMDAR-E.