Expression And Significance Of FOXP3 And GARP In Endometriosis

Objective:Our study was to investigate the Tregs infiltration and the expression of FOXP3 and GARP in endometriosis and to explore the influence of Tregs on the pathogenesis of endometriosis.We also investigated the value of FOXP3 and GARP as Tregs surface or intracellular markers and explored the role of local immune environment in the pathogenesis,diagnosis and prognosis of the patients with endometriosis to provide evidence to immunotherapy in endometriosis.Methods:A total of 48 patients with endometriosis who received surgical treatment between 2015 July and 2017 in Tianjin Central Hospital of Gynecology Obstetrics were retrospectively evaluated.The clinical stage of endometriosis,follow-up outcome were obtained from the Department of Gynecology,Tianjin Central Hospital of Gynecology Obstetrics.The stage of endometriosis was determined according to the Revised American Fertility Society(r-AFS)classification.The immunohistochemical analysis of FOXP3 and GARP,Western Blot were used to analyze the correlation between FOXP3 and GARP expression and r-AFS stage and recurrence in patients with endometriosis.Measurement data were expressed as mean ± standard deviation(±s),count data expressed as percentage.Independent sample t-test was used for independent sample results.The between-group differences in immunohistochemical staining were analyzed using Pearson's chi-squared test.Spearman's correlation analysis was used to determine the correlation between the stages of endometriosis and FOXP3+ and GARP+ Tregs in the endometriosis group.The recurrence factor was analyzed using binary logistic regression analysis methods.All two-sided P-values <0.05 were considered statistically significant.Result:1.The infiltration of FOXP3+Tregs and GARP+Tregs in the endometriosis group was significantly higher than that in the eutopic endometrium group(P <0.01 and P <0.01).2.In the endometriosis group,the infiltration of FOXP3+Tregs and GARP+Tregs in the high endometriosis stages(stage III+IV)was significantly increased compared with the low stages(stage I+II)(P=0.02,P=0.03).3.FOXP3 and GARP protein expression in high-grade endometriosis r-AFS stages was higher which is positively correlated with the r-AFS stage.The expression of FOXP3 was significantly correlated with the expression of GARP(r=0.88,P<0.01).4.GARP+Tregs infiltration and r-AFS stages were two independent prognostic factors for the recurrence of endometriosis.Patients with high infiltration of GARP+Tregs and a higher r-AFS stages had an increased risk of recurrence(P = 0.01,P = 0.01).Conclusion:1.The pelvic immune environment involve in the pathogenesis of endometriosis.The makers of Tregs FOXP3 and GARP were higher in the endometriosis tissue,which indicates that Tregs infiltration has impact on endometriosis.2.GARP and FOXP3 expression was higher in high-grade r-AFS stages endometriosis,suggesting that immune factors promote the progress of endometriosis.3.The stages of endometriosis and GARP+Tregs infiltration were independent prognostic factors for recurrence of endometriosis,confirming that GARP is more reliable makers than FOXP3 for Tregs cells.4.The immune suppression of Tregs function may be another strategy for the treatment of endometriosis in the future.