The Proportion Of Different Phenotype Regulatory B Cells In Patients With Rheumatoid Arthritis And Their Relationship With Disease Activity: A Meta-analysis

Objective:Reduced proportion of regulatory B cells?Bregs?and impaired function in peripheral blood of patients with rheumatoid arthritis?RA?may be involved in its pathogenesis.A meta-analysis method was used to systematically evaluate changes in the proportion of peripheral blood Bregs in RA patients to further clarify whether Bregs Participated in the pathogenesis of RA and its relationship with disease activity,providing new ideas for the treatment of RA.Methods:Search PubMed,Embase,The Cochrane Library,Web of Science,China Knowledge Network Database?CNKI?,Wanfang Data Knowledge Service Platform and other databases.The search time limit is from the establishment of the library to April2020.Chinese search terms include:"rheumatoid arthritis""RA""regulatory B cells""Bregs""B10 cells"and so on.The English search terms are:"Rheumatoid arthritis"and"B-Lymphocytes,Regulatory".The retrieval process uses Mesh subject words and free words.Incorporate documents that meet the standards and extract relevant outcome index data,and use the NOS scale to evaluate the quality of the documents.The extracted data was statistically processed by Review Manager 5.3 software for heterogeneity analysis,merger analysis,sensitivity analysis,and evaluation of publication bias.Results:1.A total of 7 medium-to-high-quality case-control studies were included,including719 RA patients and 335 healthy controls.The heterogeneity of the included literature was high?P<0.001,I²=98%?,and the data were combined using a random effect model.2.Meta analysis results showed that the proportion of Bregs in the peripheral blood of RA patients was significantly lower than that of the healthy control group,and the difference was statistically significant[SMD=-1.17,95%CI?-2.23,-0.10?,P<0.05];3.The proportion of peripheral blood Bregs in RA patients was negatively correlated with DAS28[r=-0.286,95%CI?-0.369,-0.198?,P<0.001].4.Compared with the healthy control group,there was no significant difference in serum IL-10 levels of RA patients[SMD=-4.94,95%CI?-10.44,0.56?,P=0.08],IL-10levels in peripheral blood Bregs cells of RA patients Decrease[SMD=-3.32,95%CI?-4.02,-2.63?,P<0.001]5.Subgroup analysis showed that the proportion of BCDs marked with"CD24^hi,CD38^hi"in the peripheral blood of RA patients was significantly lower than that of the healthy control group,and the difference was statistically significant[SMD=-1.80,95%CI?-3.48,-0.11?,P=0.04];There was no significant difference in the proportion of“CD24^hi,CD27⁺”marked Bregs in peripheral blood of RA patients and healthy controls[SMD=-0.37,95%CI?-1.36,0.61?,P=0.46]6.Sensitivity analysis After the elimination analysis of each study,there is no significant difference between the combined effects,indicating that the Meta analysis results are relatively stable.7.Qualitative evaluation of the funnel chart This Meta analysis found no obvious publication bias.Conclusion:Compared with healthy controls,the proportion of Bregs marked with CD19⁺CD24^hiCD38^hi in the peripheral blood of the RA patients and the level of intracellular IL-10 were significantly reduced.The proportion of CD19⁺CD24^hiCD38^hii Bregs in the peripheral blood of RA patients was negatively correlated with DAS28.The decrease in the proportion of CD19⁺CD24^hiCD38^hi Bregs may be one of the important links in the occurrence and development of RA,which is related to the disease activity and may be the cause of the decrease in IL-10.It can provide ideas for finding new targets for the treatment of RA,but further experiments are required To verify this conclusion.