Cytokines In Cerebrospinal Fluid Of Patients With Anti-N-methyl-D-aspartate Receptor Encephalitis

BackgroundAnti-N-methyl-D-aspartate(NMDA)receptor encephalitis is a relatively common autoimmune neurological disease of the central nervous system(CNS),mainly affecting young women.Typical clinical manifestations are hallucinations,catatonia,altered levels of consciousness,seizures,hypoventilation,dyskinesia,and autonomic.Since its discovery in 2007,anti-NMDA receptor encephalitis has become one of the most common causes of encephalitis.Magnetic resonance imaging(MRI)showed no abnormalities in 50%of patients with anti-NMDAR encephalitis.Detection of anti-NMDA receptor antibodies in serum or cerebrospinal fluid is the main basis for the diagnosis of this disease.Although the current study has a good understanding of the pathogenesis of NMDA receptor encephalitis and developed methods for detecting autoantibodies in serum and cerebrospinal fluid,the biomarkers we use to demonstrate and monitor inflammation are still very limited.As an objective indicator of quantitative detection,cytokines are involved in the whole process of T cell and B cell immune responses,so it may provide new insights into the pathogenesis of the disease,become a new biomarker against NMDA receptor encephalitis,and improve our ability to monitor the effectiveness of treatment and prognosis of the disease.ObjectiveTo search for new biomarkers in cerebrospinal fluid of patients with anti-NMDA receptor encephalitis,analyze their correlation with other clinical indicators of patients,and analyze their roles in assessing patients'condition,treatment effect and prognosis.MethodsIn order to achieve the above objectives,we conducted three parts of experiments.Clinical data and cerebrospinal fluid were collected from patients with anti-NMDA receptor encephalitis,inflammatory and non-inflammatory diseases.The levels of Pentraxin 3(PTX3),CD40 ligand(CD40L),neuron-specific enolase(NSE),S100 calcium-binding protein B(S100B),NLRP3,IL-1?,IL-6 and IL-17A in cerebrospinal fluid were detected by enzyme-linked immunosorbent assay(ELISA).The modified Rankin Scale(mRS)score was used to assess clinical outcomes.SPSS software was used for statistical analysis.ResultsCompared with the control groups,the levels of PTX3,CD40L,NSE,S100B,NLRP3 inflammatory,IL-1?,IL-6 and IL-17A in the cerebrospinal fluid of patients with anti-NMDAR encephalitis were significantly increased(p<0.05).The concentrations of PTX3 and CD40L were not related to the age and sex of the patients but were positively correlated with the mRS score.The concentrations of NSE and S100B in the early stage of the disease were significantly higher than those in the late stage and were positively correlated with the mRS score.There was no correlation between NSE and S100B concentrations and anti-NMDA receptor antibody titers.There was a positive correlation between NLRP3 inflammatory bodies in the cerebrospinal fluid and IL-1?,IL-6 and IL-17A levels.After treatment,the levels of NLRP3 inflammatory,IL-1?,IL-6,and IL-17A were significantly decreased in cerebrospinal fluid.There was a positive correlation between maximal mRS score and the level of NLRP3 inflammatory.During follow-up,?mRS was positively correlated with the reduction of the level of NLRP3 inflammatory.Conclusion:Immune responses and neuroinflammation play important roles in the pathogenesis of anti-NMDA receptor encephalitis.Neuronal damage may be associated with the onset of anti-NMDA receptor encephalitis.PTX3,CD40L,and NLRP3 inflammatory in the cerebrospinal fluid of patients with anti-NMDA receptor encephalitis can be used as biomarkers to evaluate the prognosis of patients.The level of NLRP3 inflammatory in the acute phase can be used as an indicator of the severity of anti-NMDAR encephalitis.