Levels Of Peripheral Th17 Cells And Regulatory T Cells In Patients With Multiple Sclerosis: A Meta-analysis

Objective:To ensurewhether or notTh17 cells and Regulatory T cells involved in the pathogenesis of MS patients,this study did a meta-analysis of the researches published previously to assess levelsof Th17 cells and IL-17,IL23 and regulatory T cells in patients with MS.Methods:This studycompletely searched CNKI,Wanfangdata,Embase,PubMed,Cochrane,Web of Knowledge,FDA.gov,and Clinical Trials.gov for the researches which had the results of proportion of Th17 cells,Treg and the serum levels of IL-17,IL23 in MS patients.Our main endpoints were the proportion of Th17 cells and Treg among CD4~+T cells in peripheral blood(PB),serum IL-17 levels,and serum IL-23 levels.We dealt with data by using a random-effects model.We had registered these studies at International Prospective Register of Systematic Reviews(PROSPERO)(number CRD42017059113,CRD42017064906).The evidence level of selected studies wasidentifiedby guidelines from the Oxford Center for Evidence-Based Medicine 2011.We used the Newcastle–Ottawa Quality Assessment Scale(Case Control Studies)to perform a quality assessment of researches which were included in meta-analysis.Stata 12.0 was used for dealing with the data and other statistical analysis.Results:1.Of 585 identified studies,a total 16 researches were selected in our meta-analysis.MS individuals,compared with control subjects,had a higher levels of Th17 cells[1.89,(1.10,2.69),P<0.001]in PB,an elevated levels of serum IL-17[2.77,(1.77,3.77),p<0.001]and an increased IL-23 levels in the serum[2.96(1.51,4.40),p<0.001].2.Of 1052 identified studies,a total 21 studies were selected in our meta-analysis.There was not significantly difference between MS patients and control subjects in Treg identified by all definition methods[-0.355,(-0.748,0.039),P=0.077]and Treg defined by CD4+and CD25+[0.006,(-0.452,0.440),P=0.979]MS patients,compared with control subjects,had a lower proportion of Treg defined by CD4+,CD25+and FOXP3+[-1.052,(-1.549,0.554),P<0.001]in PB.Conclusion:1.Under random effect model of meta-analysis,the data showed that the proportion of Th17 cells in PB and levels of serum IL-17 and IL-23 are increased among MS patients compared to control subjects.That result demonstrates that Th17 cells and Th17-related cytokines(IL-17,IL-23)may be engaged in the pathogenic mechanisms of MS.2.Under random effect model of meta-analysis,the data showed that the results of meta-analysis of Treg are different according to the variety of experimental Treg definition methods;and the proportion of Treg defined by CD4+,CD25+and FOXP3+is decreased in MS.That result demonstrates that FOXP3 may be a vital definition of Treg,and Treg defined by stricter definition methods may be involved in the pathogenic mechanisms of MS patients.