Cytokines/Chemokines: Potential Biomarkers For Non-Paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis

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-alpha, 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-alpha, IFN-gamma, 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.