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Front Immunol. 2019 Feb 6;10:103. doi: 10.3389/fimmu.2019.00103. eCollection 2019.

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

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Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Neurology, Randall Children's Hospital, Legacy Health, Portland, OR, United States.
Department of Surgical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, United States.
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Legacy Health, Portland, OR, United States.


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.


IL-10; IL-6; TNF-α; anti-NMDAR encephalitis; cell-free mitochondrial DNA; cerebrospinal fluid; cytokines; modified rankin scale

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