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血清ALKBH5、FKBP5与复发性流产患者Th17/Tregs失衡及保胎结局的关联性研究
李 晶1,郭 洁1,汤丽丽2
1.邯郸市第一医院生殖内分泌科,邯郸 056002;2.邯郸市妇幼保健院生殖医学科,邯郸 056001
摘要:
[摘要] 目的 探讨血清ALKB同源蛋白5(ALKBH5)、FK506结合蛋白5(FKBP5)与复发性流产(RSA)患者Th17/Tregs失衡及保胎结局的关联性。方法 招募2022年1月至2024年1月邯郸市第一医院收治的100例RSA患者(RSA组),选择同期无不良妊娠史的健康孕妇100名作为对照组。根据RSA患者保胎结局将其分为保胎成功组(67例)和保胎失败组(33例)。采用酶联免疫吸附试验(ELISA)检测研究对象血清ALKBH5、FKBP5水平。通过流式细胞术检测外周血Th17、Tregs水平,并计算Th17/Tregs比值。采用Pearson相关分析血清ALKBH5、FKBP5水平与Th17、Tregs、Th17/Tregs比值水平的相关性。采用多因素logistic回归分析影响RSA患者保胎失败的因素。采用受试者工作特征(ROC)曲线分析血清ALKBH5、FKBP5对RSA患者保胎失败的预测效能。结果 RSA组血清ALKBH5、Tregs水平低于对照组,FKBP5、Th17、Th17/Tregs比值水平高于对照组,差异有统计学意义(P<0.05)。Pearson相关分析结果显示,RSA患者血清ALKBH5水平与Th17、Th17/Tregs比值呈负相关(P<0.05),与Tregs水平呈正相关(P<0.05);血清FKBP5水平与Th17、Th17/Tregs比值呈正相关(P<0.05),与Tregs水平呈负相关(P<0.05)。多因素logistic回归分析结果显示,较高的Th17/Tregs比值[OR(95%CI)=2.327(1.050~5.157),P=0.038]、FKBP5[OR(95%CI)=3.145(1.351~7.320),P=0.008]水平是RSA患者保胎失败的独立危险因素(P<0.05),较高的ALKBH5水平[OR(95%CI)=0.205(0.071~0.594),P=0.004]是抑制RSA患者保胎失败发生的独立保护因素(P<0.05)。ROC曲线分析结果显示,血清ALKBH5、FKBP5两指标联合预测RSA患者保胎失败的效能较单一指标更高(Z两指标联合-ALKBH5=2.092,P=0.036;Z两指标联合-FKBP5=2.451,P=0.014),灵敏度为96.97%,特异度为73.13%。结论 RSA患者血清ALKBH5水平降低,FKBP5水平升高,二者异常表达可能与Th17/Tregs失衡、保胎失败有关。
关键词:  复发性流产  ALKB同源蛋白5  FK506结合蛋白5  Th17/Tregs失衡  保胎结局
DOI:10.3969/j.issn.1674-3806.2026.04.10
分类号:R 714.21
基金项目:
Study on association of serum ALKBH5 and FKBP5 with Th17/Tregs imbalance and tocolysis outcomes in patients with recurrent spontaneous abortion
LI Jing1, GUO Jie1, TANG Lili2
1.Department of Reproductive Endocrinology, Handan First Hospital, Handan 056002, China; 2.Department of Reproductive Medicine, Handan Maternal and Child Health Hospital, Handan 056001, China
Abstract:
[Abstract] Objective To explore the association of serum ALKB homolog 5(ALKBH5) and FK506-binding protein 5(FKBP5) with T helper cells 17(Th17)/regulatory T cells(Tregs) imbalance and tocolysis outcomes in patients with recurrent spontaneous abortion(RSA). Methods One hundred patients with RSA who were admitted to Handan First Hospital from January 2022 to January 2024 were recruited as RSA group, and 100 healthy pregnant women without an adverse pregnancy history during the same period were selected as control group. According to tocolysis outcomes of the RSA patients, they were divided into successful tocolysis group(67 patients) and failed tocolysis group(33 patients). The levels of serum ALKBH5 and FKBP5 in the research subjects were detected by using enzyme-linked immunosorbent assay(ELISA). The levels of Th17 and Tregs in the peripheral blood were detected by using flow cytometry, and the Th17/Tregs ratio was calculated. Pearson correlation was used to analyze the correlations of serum ALKBH5 and FKBP5 levels with Th17, Tregs and Th17/Tregs ratio levels. Multivariate logistic regression was used to analyze the factors influencing the failed tocolysis in the RSA patients. Receiver operating characteristic(ROC) curve was used to analyze the efficacy of serum ALKBH5 and FKBP5 for predicting the failed tocolysis in the RSA patients. Results The levels of serum ALKBH5 and Tregs in the RSA group were lower than those in the control group, while the levels of FKBP5, Th17, and Th17/Tregs ratio in the RSA group were higher than those in the control group, with statistically significant differences between the two groups(P<0.05). The results of Pearson correlation analysis showed that in the RSA patients the serum ALKBH5 level was negatively correlated with Th17 and Th17/Tregs ratio(P<0.05), and was positively correlated with Tregs level(P<0.05); serum FKBP5 level was positively correlated with Th17 and Th17/Tregs ratio(P<0.05), and was negatively correlated with Tregs level(P<0.05). The results of multivariate logistic regression analysis showed that higher Th17/Tregs ratio[OR(95%CI)=2.327(1.050-5.157), P=0.038] and higher FKBP5 level[OR(95%CI)=3.145(1.351-7.320), P=0.008] were independent risk factors for failed tocolysis in the RSA patients(P<0.05), and higher ALKBH5 level[OR(95%CI)=0.205(0.071-0.594), P=0.004] was an independent protective factor for inhibiting the occurrence of failed tocolysis in the RSA patients(P<0.05). The results of ROC curve analysis showed that the efficacy of serum ALKBH5 combined with FKBP5 in predicting failed tocolysis in the RSA patients was higher than that of a single indicator(Zcombination of the two indicators- ALKBH5=2.092, P=0.036; Zcombination of the two indicators- FKBP5=2.451, P=0.014), with a sensitivity of 96.97% and a specificity of 73.13%. Conclusion Serum ALKBH5 level decreases and serum FKBP5 level increases in RSA patients, and the abnormal expressions of both indicators may be related to Th17/Tregs imbalance and failed tocolysis.
Key words:  Recurrent spontaneous abortion(RSA)  ALKB homolog 5(ALKBH5)  FK506-binding protein 5(FKBP5)  Th17/Tregs imbalance  Tocolysis outcomes