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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.

Author information

1
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
2
Department of Neurology, the Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China.
3
Department of Neurology, Randall Children's Hospital, Legacy Health, Portland, OR, United States.
4
Department of Surgical Oncology, MD Anderson Cancer Center, University of Texas, Houston, TX, United States.
5
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Legacy Health, Portland, OR, United States.

Abstract

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.

KEYWORDS:

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

PMID:
30792710
PMCID:
PMC6375341
DOI:
10.3389/fimmu.2019.00103
[Indexed for MEDLINE]
Free PMC Article

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