Changes and Significance of Follicular Helper T Cells and Their Cytokines in Peripheral Blood and Endometrium of Patients with Unexplained Recurrent Im-plantation Failure
Objective:To investigate the changes in follicular helper T cells(Tfh)and related cytokines in pe-ripheral blood and endometrial tissue of patients with unexplained recurrent implantation failure(URIF),and evalu-ate their predictive value for URIF.Methods:Sixty-four patients with URIF who visited the Reproductive Medicine Centre of the First Affiliated Hospital of Xinjiang Medical University from December 2020 to June 2022 were select-ed as the study group(URIF group),and 61 healthy women of childbearing age who visited our centre for male in-fertility in the same period were selected as the healthy control group(HC group).GSE microarrays of patients with recurrent implant failure(RIF)were collected in the Gene Expression Omnibus(GEO)database,and the pro-portion of different immune cells was identified using the CIBERSORT algorithm,and immune cell infiltration analy-sis and visualisation processing were performed using the Cibersort.R package.Peripheral blood samples and endometrial tissue samples were collected from the two groups of patients,flow cytometry was used to detect the proportion of Tfh cells in peripheral blood,enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of IL-4,IL-6,and IL-21,and immunohistochemical staining was used to detect the expression of CXCR5,Bcl-6,and IL-21 in endometrial tissue.Factors associated with URIF were analysed using multifactorial Logistic re-gression analysis.The predictive value of individual and combined tests for each indicator for URIF was analysed using the operating characteristic curve(ROC).The Drug Therapy Target Database(TTD)was used to predict potential therapeutic agents for URIF targeting IL-6 and IL-21,respectively.Results:The results of immune cell in-filtration in the GSE dataset in the GEO database showed that compared with normal controls,the numbers of ac-tivated memory CD4+T cells,Tfh,regulatory T cells(Treg),inactive macrophages,and resting dendritic cells were increased in the endometrial tissues of the patients with RIF(P＜0.05).The number of initial B cells,yδT cells,M2-type macrophages and activated dendritic cells were all decreased(P＜0.05).The levels of peripheral blood Tfh,IL-6 and IL-21 in the URIF group were all significantly higher than those in the HC group,and the difference was statistically significant(P＜0.05).Immunohistochemical staining results suggested that the expression of CX-CR5,Bcl-6 and IL-21 in the endometrium of patients in the URIF group was increased compared with that in the HC group(P＜0.05).Multivariate Logistic regression analysis showed that IL-6,IL-2,and Tfh were independent risk factors for the occurrence of URIF(OR＞1,P＜0.05).The area under the curve(AUC=0.974)of peripheral blood Tfh combined with IL-6 and IL-21 for diagnosis of URIF was higher than that predicted by each index alone,according to ROC analysis(P＜0.05).Five drugs targeting IL-6 or IL-21 with potential therapeutic effects on URIF were detected and screened through the TTD database.Conclusions:The levels of Tfh,IL-6 and IL-21 in the pe-ripheral blood of patients with URIF were abnormally elevated,and CXCR5,Bcl-6 and IL-21 were abnormally ex-pressed in the endometrium of patients with URIF,suggesting that Tfh cells and their cytokines are closely related to the occurrence and development of URIF.The combined prediction of these indicators has good diagnostic val-ue and may serve as a therapeutic target.
Recurrent implantation failureFollicular helper T celllmmune infiltration analysisPrediction
万方数据
维普
