The Proportion Of Regulatory T Cells In Patients With Primary Sjogren’s Syndrome:A Meta-Analysis

Background and objective:More and more evidence has shown that regulatory T cells(Tregs)may play a very important role in the pathogenesis of primary Sjogren’s Syndrome(p SS).However,these studies on the proportion of Tregs in peripheral blood(PB)of patients with p SS are inconclusive due to differences in the surface markers of Tregs.In order to systematically evaluate the state of Tregs in these patients,we performed a Meta-analysis to clarify the proportion of Tregs in PB of patients with p SS and its relationship with the phenotypes of different Tregs.Methods:The Pub Med,Web of Science,Cochrane Library and Embase were systematically searched to obtain observational studies on the proportion of Tregs in p SS patients from the establishment of the database to December 2022.Newcastle-Ottawa Quality Assessment Scale(NOS)and Agency for Healthcare Research and Quality(AHRQ)cross-sectional study evaluation criteria were used to evaluate the quality of the included studies.Meta-analysis on the frequency of Tregs with different phenotypes in PB was carried out by using Stata 12.0 software.Heterogeneity test was evaluated by the I-squared index(I~2)and P value.And evaluation of publication bias was performed by using the Egger test funnel plot asymmetry.Results:A total of 10 articles were included in this study,including 17 studies involving291 patients with p SS and 283 healthy controls.The results of Meta-analysis on the proportion of Tregs in PB,peripheral blood mononuclear cells(PBMC)and CD4~+T cells in patients with p SS showed that:compared with the healthy control group,the proportion of Tregs in PB,PBMC and CD4~+T cells was similar in the p SS group,and the difference was not statistically significant[SMD=-0.007,95%CI(-0.589,0.575),P<0.001,I~2=92.9%;SMD=-1.040,95%CI(-3.183,1.102),P<0.001,I~2=98.0%;SMD=0.217,95%CI(-0.158,0.593),P<0.001,I~2=78.8%].After that,Tregs were divided into CD4~+CD25~+Tregs group,CD4~+FOXP3~+Tregs group and CD4~+CD127~-Tregs group.In the data extraction process of PBMC Tregs group,only CD4~+CD25~+Tregs could be subgroup analyzed.The results suggested that compared with the healthy control group,the proportion of CD4~+CD25~+Tregs in the PBMC of p SS patients was significantly reduced,and the difference was statistically significant[SMD=-2.011,95%CI(-3.934,-0.088),P<0.001,I~2=96.5%].Subgroup analysis of Tregs in CD4~+Tregs group with CD25~+,FOXP3~+and CD127~-as surface markers was conducted,and the results suggested that:compared with the healthy control group,the proportion of CD4~+FOXP3~+Tregs in patients with p SS was significantly higher,and the difference was statistically significant[SMD=0.489,95%CI(0.230,0.748),P=0.131,I~2=43.6%].There was no significant difference in the proportion of CD4~+CD25~+Tregs and CD4~+CD127~-Tregs between healthy control groups[SMD=-0.209,95%CI(-0.814,0.396,P<0.001,I~2=83.5%;SMD=0.301,95%CI(-0.314,0.917),P=0.216,I~2=34.7%].A Meta-analysis was conducted to investigate the relationship between the presence of extrandular involvement in p SS patients and the proportion of Tregs in PB.The results showed that compared with the glandular limited p SS patients,the proportion of Tregs in PB in p SS patients with extrandular involvement was higher,and the difference was statistically significant[SMD=0.699,95%CI(0.107,1.291),P=0.567,I~2=0%].Conclusion:1.The proportion of Tregs in PB,PBMC and CD4~+T cells was similar in the p SS patients,while the proportion of CD4~+CD25~+Tregs in PBMC and CD4~+T cells was different.2.The proportion of CD4~+FOXP3~+Tregs in CD4~+T cells in p SS patients increased significantly,and FOXP3~+was recommended as a surface marker of Tregs to identify Tregs in p SS patients.3.Compared with patients with glandular p SS,the proportion of Tregs in PB increased in patients with p SS with different external organ involvement,further confirming the theory of reverse distribution of Tregs in labial glandular tissue and PB.