Abstract
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.
Highlights
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis, accounting for about 80% of patients [1]
The detailed clinical presentations and MRI, EEG, and Cerebrospinal fluid (CSF) findings are shown in Supplementary Table 1
Comparison of the Levels of Cytokines/Chemokines Between Patients With Anti-NMDAR Encephalitis and Controls Statistical analysis showed that the levels of IFN-γ (P = 0.001), TNF-α (P < 0.001), CXCL10 (P = 0.001), CCL3 (P = 0.001), CCL1 (P = 0.001), CCL8 (P = 0.007), CCL17 (P = 0.005), CCL22 (P < 0.001), IL-7 (P = 0.005), CXCL13 (P = 0.001), IL-10 (P = 0.002), IL-12 p40 (P = 0.002), and IL-16 (P = 0.004) in CSF were significantly increased in patients with anti-NMDAR encephalitis compared to those of controls (Figure 1)
Summary
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis, accounting for about 80% of patients [1]. Dalmau and colleagues described the clinical characteristics of anti-NMDAR encephalitis, which is caused by specific immunoglobulin G (IgG) antibodies against NMDAR on the neuron membrane [2]. The antibodymediated progressive deficiency of NMDAR and the gradual recovery of receptor function with decreased antibody titer may be the cause of aggravation and remission of the disease, respectively [3]. Antibody titer can reflect the severity of the disease, but this has some limitations. Continuous intrathecal synthesis of antibody does not necessarily indicate that encephalitis is in the active phase. Antibody titers do not change significantly when clinical symptoms are alleviated and can remain positive even after complete recovery [4, 5]. Cerebrospinal fluid (CSF) markers including cytological examination, oligoclonal banding, and CSF-IgG synthesis rate lack sensitivity and specificity
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