The Proportion Of Regulatory T Cells And Th17 Cells In Patients With Ankylosing Spondylitis: A Meta-Analysis

Objective:Accumulating evidence indicates that regulatory T cells?Tregs?may be involved in the pathogenesis of ankylosing spondylitis?AS?.To explore whether Treg cells and Th17cells were involved in the pathogenesis of AS,this study systematically review the proportion of Treg cells with different cellular markers,the proportion of Th17 cells and some cytokines in peripheral blood of patients with AS.Methods:PubMed,EMbase,The Cochrane Library,CNKI,WanFang Data and VIP databases were electronically searched to collect case-control studies about peripheral Treg cells and Th17 cells of AS patients from inception to February 1^st,2020.Two reviewers independently screened literature,extracted data and assessed the risk of bias of included studies.Then,meta-analysis was performed by using Stata 12.0 software.Results:1.A total of 58 case-control studies about peripheral Treg cells involving 2372 AS patients and 1706 controls were included.The results of meta-analysis showed that:the proportion of peripheral Treg cells of patients with AS was significantly lower than that of the normal control?SMD=-0.968,95%CI-1.376 to-0.560,P<0.001?,and the proportion of Treg cells in the disease-active group was significantly lower than that in the disease-inactive group?SMD=-0.928,95%CI-1.431 to-0.425,P<0.001?.The proportion of CD4⁺CD25^+/highFOXP3⁺Treg cells and CD4⁺CD25⁺CD127^low/-Treg cells were lower in AS patients than that in control subjects?SMD=-2.811,95%CI-3.913 to-1.709,P<0.001;SMD=-0.710,95%CI-1.025 to-0.396,P<0.001?.The proportion of Tregs defined by CD4⁺CD25^low/-FOXP3⁺was higher in AS patients?SMD=0.683,95%CI 0.161 to 1.206,P=0.01?.2.A total of 47 case-control studies on the proportions of peripheral Th17 cells and cytokines in peripheral blood of AS patients were included,including 2231 AS patients and1389 healthy controls.The results of meta-analysis showed that:the proportion of peripheral Th17 cells of patients with AS was significantly higher than that of the normal control?SMD=3.005,95%CI 2.439 to 3.571,P<0.001?.Compared with the control group,the levels of IL-17,IL-23,IL-6,TNF-?in peripheral blood of AS patients were significantly increased?SMD=2.895,95%CI 2.076 to 3.714,P<0.001;SMD=3.195,95%CI 2.176 to 4.215,P<0.001;SMD=4.068,95%CI 2.935 to 5.202,P<0.001;SMD=7.633,95%CI 5.009 to 10.258,P<0.001?.There was no significant difference in the level of TGF-?between the two groups.Conclusion:1.The reduction of Tregs may be one of the important reasons for the occurrence and development of AS.And we recommend CD4⁺CD25^+/highFOXP3⁺or CD4⁺CD25⁺CD127^low/-as the best definition of Treg cells to more accurately identify peripheral blood Treg cells.2.Th17 cells may synergistically regulate various inflammatory cytokines in AS patients,which may play an important role in the pathogenesis and prognosis of AS.