外周血Foxp3、RANTES联合检测对原因不明复发性流产的临床诊断价值

The clinical diagnostic value of combined detection of peripheral blood Foxp3 and RANTES for unexplained recurrent miscarriage

目的探讨外周血叉头框蛋白p3(Foxp3)、T细胞正常表达和分泌刺激因子(RANTES)联合检测对原因不明复发性流产的临床诊断价值。方法选择2021年7月至2022年9月本院收治的128例原因不明复发性流产患者为病例组,另选取同期于本院体检的128例健康早孕者为对照组。采用酶联免疫吸附试验(ELISA)检测所有研究对象外周血的Foxp3和RANTES水平,流式细胞仪检测外周血辅助性T细胞(Th17)和调节性T细胞(Treg)水平。采用Pearson和Spearman相关性分析法分析外周血Foxp3和RANTES水平与免疫指标和原因不明复发性流产的相关性;采用受试者工作特征(ROC)曲线分析外周血Foxp3和RANTES水平对原因不明复发性流产的诊断价值。结果与对照组比较,病例组外周血Foxp3、RANTES水平和Treg比例显著下降(P<0.05),Th17比例和Th17/Treg显著升高(P<0.05)。Pearson相关性分析结果显示,病例组外周血Foxp3和RANTES水平与Th17、Th17/Treg均呈显著负相关(P<0.05),与Treg均呈显著正相关(P<0.05);Spearman相关性分析结果显示,外周血Foxp3和RANTES水平均与原因不明复发性流产的发生呈显著负相关(r=-0.539,-0.554,P<0.05)。ROC曲线结果显示,血清Foxp3水平单独诊断原因不明复发性流产发生的曲线下面积(AUC)为0.820[95%CI(0.767,0.865)],其敏感度、特异度分别为70.31%、85.94%;血清RANTES水平单独诊断原因不明复发性流产发生的AUC为0.840[95%CI(0.789,0.883)],其敏感度、特异度分别为69.53%、85.16%;血清Foxp3和RANTES联合诊断原因不明复发性流产发生的AUC为0.909[95%CI(0.867,0.942)],显著大于Foxp3单独诊断的AUC(Z=4.165,P=0.000)和RANTES单独诊断的AUC(Z=3.183,P=0.002)。结论Foxp3和RANTES水平均与原因不明复发性流产孕妇的免疫平衡失调有关,二者联合对原因不明复发性流产具有较高的诊断价值。

Objective:To explore the clinical diagnostic value of combined detection of peripheral blood forkhead box protein p3(Foxp3),regulation on activation normal T-cell expressed and secreted(RANTES)for unexplained recurrent miscarriage.Methods:A retrospective study was conducted on 128 patients with unexplained recurrent miscarriage admitted to the First Hospital of Zhangjiakou from July 2021 to September 2022.And 128 healthy women with early pregnancy who underwent physical examination were regarded as the control.Enzyme linked immunosorbent assay(ELISA)was applied to detect Foxp3 and RANTES levels,and flow cytometry was used to detect the percentages of T helper cell(Th17)and regulatory T cells(Treg)in peripheral blood.The Pearson and Spearman correlation analyses were conducted to analyze the correlation between peripheral blood Foxp3 and RANTES levels,immune indicators and unexplained recurrent miscarriage.The diagnostic value of peripheral blood Foxp3 and RANTES levels for unexplained recurrent miscarriage was evaluated with the receiver operating characteristic(ROC)curve.Results:Compared with the control group,the peripheral blood Foxp3 and RANTES levels as well as Treg ratio in the study group were obviously lower(P<0.05),while the percentage of Th17 and Th17/Treg ratio were obviously higher(P<0.05).The results of Pearson correlation analysis showed that the levels of Foxp3 and RANTES in peripheral blood of patients in the study group were obviously negatively correlated with the percentage of Th17 and Th17/Treg ratio(P<0.05),and obviously positively correlated with the percentage of Treg(P<0.05).The results of Spearman correlation analysis showed that the levels of Foxp3 and RANTES in peripheral blood were obviously negatively correlated with the occurrence of unexplained recurrent miscarriage(r=-0.539,-0.554,P<0.05).The analysis of ROC curve showed that the AUC of serum Foxp3 level alone in diagnosing unexplained recurrent abortion was 0.820[95%CI(0.767,0.865)],and its sensitivity and specificity were 70.31%and 85.94%respectively.And the AUC of unexplained recurrent miscarriage diagnosed solely by serum RANTES level was 0.840[95%CI(0.789,0.883)],with sensitivity and specificity of 69.53%and 85.16%,respectively.In addition,the AUC of unexplained recurrent miscarriage diagnosed by the combination of serum Foxp3 and RANTES levels was 0.909[95%CI(0.867,0.942)],which was obviously higher than those diagnosed by Foxp3 level alone(Z=4.165,P=0.000)and RANTES level alone(Z=3.183,P=0.002).Conclusions:The levels of Foxp3 and RANTES are associated with immune imbalance in pregnant women with unexplained recurrent miscarriage,and their combined detection results might have high diagnostic value for unexplained recurrent miscarriage.