Frontiers in Neurology (Dec 2020)

Cytokines/Chemokines: Potential Biomarkers for Non-paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis

  • Jingwen Liu,
  • Lei Liu,
  • Wenting Kang,
  • Gongxin Peng,
  • Di Yu,
  • Qiuying Ma,
  • Yatong Li,
  • Yan Zhao,
  • Lin Li,
  • Feifei Dai,
  • Jiawei Wang,
  • Jiawei Wang

DOI
https://doi.org/10.3389/fneur.2020.582296
Journal volume & issue
Vol. 11

Abstract

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Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study focuses on finding new biomarkers to evaluate the clinical condition and provide new directions for treatment.Methods: A total of 44 cytokines/chemokines in the cerebrospinal fluid of 10 non-paraneoplastic patients and nine controls were measured. We selected some of the cytokines/chemokines that significantly increased in patients. Six selected cytokines/chemokines, including IL-10, CXCL10, CCL22, CCL3, IL-7, TNF-α, and three previously reported (IL-2, IL-6, and IL-17A), were measured in seven other patients who provided repeat samples. We compared their levels and explored correlations with severity of disease and antibody titers.Results: The levels of Th1 axis (CXCL10, TNF-α, IFN-γ, CCL3), Th2 axis (CCL1, CCL8, CCL17, CCL22), Treg axis (IL-10), Th17 axis (IL-7), and B cell axis (CXCL13) cytokines, as well as IL-12 p40 and IL-16, were significantly higher in patients compared to those in controls. The level of IL-2 was significantly decreased at the intermediate stage of treatment compared with that before treatment. The severity of disease is positively correlated with levels of CXCL10, CCL3, IL-10, CCL22, and IL-6. The level of CCL3 in the high antibody titer group was greater than that in the low antibody titer group.Conclusion: The pathogenesis of anti-NMDAR encephalitis involves T cell and B cell cytokines. T cells likely assist B cells to produce antibodies. IL-2, CXCL10, CCL3, IL-10, CCL22, and IL-6 may represent new biomarkers in anti-NMDAR encephalitis. Given the lack of research on IL-10, CCL3, and CCL22 in this disease, it will be informative to explore their potential role in pathogenesis in larger studies.

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