Data_Sheet_1_Cell-Free Mitochondrial DNA in the CSF: A Potential Prognostic Biomarker of Anti-NMDAR Encephalitis.docx

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune inflammatory brain disease that can develop a variety of neuropsychiatric presentations. However, the underlying nature of its inflammatory neuronal injury remains unclear. Mitochondrial DNA (mtDNA) is recently regarded as a damage-associated molecular pattern molecule (DAMP) that can initiate an inflammatory response. In the presenting study, we aimed to evaluate the levels of cell-free mtDNA in cerebrospinal fluid (CSF) of patients with anti-NMDAR encephalitis and to determine a potential role of cell-free mtDNA in the prognosis of anti-NMDAR encephalitis. A total of 33 patients with NMDAR encephalitis and 17 patients with other non-inflammatory disorders as controls were included in this study. The CSF levels of cell-free mtDNA were measured by quantitative polymerase chain reaction (qPCR). Cytokines including interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNF-α) were measured by ELISA. The modified Rankin scale (mRS) score was evaluated for neurologic disabilities. Our data showed that the CSF levels of cell-free mtDNA and inflammation-associated cytokines were significantly higher in the patients with anti-NMDAR encephalitis compared with those in controls. Positive correlations were detected between the CSF levels of cell-free mtDNA and mRS scores of patients with anti-NMDAR encephalitis at both their admission and 6-month follow up. These findings suggest that the CSF level of cell-free mtDNA reflects the underlying neuroinflammatory process in patients with anti-NMDAR encephalitis and correlates with their clinical mRS scores. Therefore, cell-free mtDNA may be a potential prognostic biomarker for anti-NMDAR encephalitis.

抗N-甲基-D-天冬氨酸受体（NMDAR）脑炎是一种可出现多种神经精神表现的自身免疫性炎性脑病，但其炎性神经元损伤的潜在机制仍未明确。线粒体DNA（mtDNA）近来被认为是可启动炎症应答的损伤相关分子模式分子（DAMP）。本研究旨在检测抗NMDAR脑炎患者脑脊液（CSF）中的游离线粒体DNA水平，并探讨游离线粒体DNA在抗NMDAR脑炎预后中的潜在作用。本研究共纳入33例抗NMDAR脑炎患者，以及17例其他非炎性疾病患者作为对照。采用实时定量聚合酶链反应（qPCR）检测脑脊液中游离线粒体DNA水平；采用酶联免疫吸附试验（ELISA）检测白细胞介素（IL）-6、IL-10及肿瘤坏死因子α（TNF-α）等细胞因子水平；采用改良Rankin量表（mRS）评估患者的神经功能残疾程度。结果显示，与对照组相比，抗NMDAR脑炎患者脑脊液中的游离线粒体DNA及炎症相关细胞因子水平显著升高。在患者入院时及6个月随访时，脑脊液游离线粒体DNA水平均与患者的mRS评分呈显著正相关。上述结果表明，脑脊液游离线粒体DNA水平可反映抗NMDAR脑炎患者的神经炎症过程，并与临床mRS评分相关。因此，游离线粒体DNA或可成为抗NMDAR脑炎的潜在预后生物标志物。