Dynamic Distribution Of Circulating B Cell Subtypes And Correlation Research In Autoimmune Encephalitis

Background:Autoimmune encephalitis（AE）is a type of disease in central nervous system mediated by autoantibodies.Abnormal autoimmune system lead to antibody production against anti-neuronal cell-associated antigens,which can lead to neuronal dysfunction through various mechanisms such as cross-linking internalization.Patients with AE manifeste as seizures,cognitive impairment,mental behavioral abnormalities,disturbance of consciousness,involuntary movements,and autonomic dysfunction with multiple acute or subacute onset.B cells occupy a central position in the pathogenesis of AE based on the pathogenic antibodies.The successful application of"B cell deletion therapy"such as rituximab further confirms the important role of B cells in the pathogenesis of AE.Regulatory B cells（Bregs）is a special type of B cell which can exert immunosuppressive effects by secreting IL-10,IL-35（Interleukin-10）and transforming growth factor-β（TGF-β）.Memory B cells（Bmems）have specific recognition for antigens.When second attack of the same antigen,they can directly proliferate and differentiate into plasma cells which can specific produce antibodies.It have also been shown to be involved in the pathogenesis of many autoimmune diseases.Multiple evidences suggest that B cells are inextricably linked to the pathogenesis of AEs.Objective:We aim to analyze the changes of B cells and subsets including regulatory B cells（Bregs）and memory B cells（Bmems）in patients with AE in acute phase and after first-line immunotherapy and explore the relation between them and disease severity.Methods:Sixteen patients with AE in the acute phase and twenty age-and gender-matched healthy controls were enrolled in this study.The percentages of CD19⁺ B lymphocytes,CD 19⁺CD24^hiCD38^hi Bregs,CD 19⁺CD24^hiCD27⁺Bregs and CD19⁺CD27⁺Bmems were evaluated in parallel by flow cytometry.The proportion of peripheral B cell subtypes for 9 patients with anti-N-methyl-aspartate receptor（NMDAR）encephalitis were analyzed before and after first-line immunotherapy.Results:（1）The frequency of CD19⁺B lymphocytes in peripheral was increased（P=0.001）in acute AE patients than in healthy controls,CD19⁺CD24^hiCD38^hiBregs%out of CD19 B lymphocytes was decreased（P<0.001）and frequencies of both CD 19⁺CD24^hiCD27⁺Bregs and CD19⁺CD27⁺Bmems have no significant differences.（2）The frequency of CD19 B lymphocytes in peripheral of patients with anti-NMDAR encephalitis was higher than that of the other two AEs（P=O.017）,and there was no significant correlation between other B cell subtypes and antibody classification.（3）The proportion of CD19⁺CD24^hiCD38^hiBregs was significantly elevated after the first-line immunotherapy.（4）CD19⁺ B lymphocytes%was positively correlated with the disease severity（r=0.607;P=0.015）while CD19⁺CD24^hiCD38^hiBregs%was negatively correlated with disease severity（r=-0.627,P=0.O11）.In the ROC curve,severe AE was defined as mRS>3.The best CD 19⁺ B lymphocytes%cut-off value to predict severe disease activity of AE was 16.76%with a sensitivity of 75%,specificity of 100%.The area under curve（AUC）was 0.917（95%CI:0.771-1.000;P=0.015）.Conclusion:Activation of B cells is a key link in the pathogenesis of autoimmune encephalitis.The peripheral humoral immune system of patients with autoimmune encephalitis is abnormally active,and the function of regulatory B cells in the body is impaired.The proportion of CD19⁺B lymphocytes and CD19⁺CD24^hiCD38^hiBregs are possible indicators for monitoring disease severity of AE and treatment response of anti-NMDAR encephalitis.