T淋巴细胞线粒体功能与抗NMDAR脑炎疾病进程的相关性研究

马玉雯; 张尔狄; 曹霖; 王祉茵; 王旻晋; 李峰; 应斌武; 严琳

doi:10.12182/20260360605

T淋巴细胞线粒体功能与抗NMDAR脑炎疾病进程的相关性研究

Association Between T Lymphocyte Mitochondrial Function and Disease Activity in Anti-NMDAR Encephalitis

摘要

摘要:
目的探讨抗NMDAR脑炎（anti-N-methyl-D-aspartate receptor encephalitis, NMDAR-E）患者T淋巴细胞线粒体功能变化特征及其与免疫耗竭状态的相关性。
方法本研究纳入2025年1–3月在四川大学华西医院神经内科确诊的抗NMDAR脑炎患者25例（轻症14例，重症11例）及健康对照16名，采用流式细胞术检测患者外周血与脑脊液中免疫细胞分布，评估低线粒体膜电位细胞比例（low mitochondrial membrane potential, MMP-Low%）、线粒体质量（mitochondrial mass, MM）及PD-1表达水平。
结果重症患者脑脊液中CD3⁺和CD4⁺T细胞占比、CD3⁺、CD4⁺和CD8⁺T细胞的MMP-Low%以及CD3和CD8⁺T细胞的MM均高于配对外周血(均P<0.05)。相比于健康对照，患者外周血CD4⁺和CD8⁺初始T细胞和中央记忆T细胞亚群MMP-Low%下降（P<0.05），同时CD4⁺初始T细胞和中央记忆T细胞亚群的PD-1阳性细胞比例上升（P<0.01）。
结论抗NMDAR脑炎患者脑脊液T细胞处于功能障碍性线粒体积聚状态，提示中枢炎症环境下T细胞线粒体质量稳态调控机制失衡。外周T细胞线粒体状态提示存在系统性免疫耗竭。脑脊液CD8⁺T细胞MMP-Low%和外周血淋巴细胞占比可作为区分抗NMDAR-E脑炎患者病情轻重的潜在免疫代谢标志物。

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.

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