不明原因复发性流产再次妊娠患者血清1,25(OH)2D3、sTim-3与Th17/Treg免疫失衡和妊娠结局的关系

摘要 目的：探讨不明原因复发性流产（URSA）再次妊娠患者血清1,25-二羟维生素D31,25（OH)）₂D₃]、可溶性T细胞免疫球蛋白黏蛋白分子3（sTim-3）与辅助性T细胞17（Th17）/调节性T细胞（Treg）免疫失衡和妊娠结局的关系。方法：选择于湖南省妇幼保健院2020年1月~2022年1月就诊的62例URSA再次妊娠患者作为研究组，另选择同期进行孕检的正常早孕妇女30例作为对照组。比较两组孕早期血清1,25(OH) ₂D₃、sTim-3及外周血Th17细胞、Treg细胞水平、Th17/Treg比值。Pearson法分析URSA再次妊娠患者血清1,25(OH) ₂D₃、sTim-3与外周血Th17细胞、Treg细胞水平、Th17/Treg比值平的相关性。根据URSA再次妊娠患者妊娠结局的不同分为妊娠成功分娩组和妊娠再次流产组，比较两组孕早期血清1,25(OH) ₂D₃、sTim-3与外周血Th17细胞、Treg细胞水平、Th17/Treg比值。受试者工作特征（ROC）曲线分析血清1,25(OH) ₂D₃、sTim-3与外周血Th17细胞、Treg细胞水平、Th17/Treg比值对妊娠结局的预测价值。结果：研究组血清sTim-3、外周血Th17细胞水平、Th17/Treg比值高于对照组，血清1,25(OH) ₂D₃、外周血Treg细胞水平低于对照组（P<0.05）。Pearson相关分析显示，URSA再次妊娠患者血清1,25(OH) ₂D₃与血清sTim-3、外周血Th17细胞水平、Th17/Treg比值呈负相关，与Treg细胞水平呈正相关（P<0.05）；血清sTim-3与外周血Treg细胞水平呈负相关，与Th17细胞水平、Th17/Treg比值呈正相关（P<0.05）。妊娠再次流产组血清sTim-3、外周血Th17细胞水平、Th17/Treg比值高于妊娠成功分娩组，血清1,25(OH) ₂D₃、外周血Treg细胞水平低于妊娠成功分娩组（P<0.05）。ROC曲线分析显示，血清1,25(OH) ₂D₃、sTim-3及外周血Th17细胞、Treg细胞水平及Th17/Treg比值均可预测URSA再次妊娠患者妊娠再次流产的发生风险，且上述指标联合检测的预测效能更高。结论：血清1,25(OH) ₂D₃水平异常降低、sTim-3水平异常升高可导致Th17/Treg免疫失衡，导致URSA再次妊娠患者再次发生流产。上述指标联合检测对URSA再次妊娠患者妊娠再次流产的预测效能更高。

Relationship between Serum 1,25(OH)2D3, sTim-3, Th17/Treg Immune Imbalance and Pregnancy Outcome in Patients with Recurrent Abortion of Unknown Cause

ABSTRACT Objective: To investigate the relationship between serum 1,25-dihydroxyvitamin D3 1,25(OH) ₂D₃], soluble T cell immunoglobulin mucin molecule 3 (sTim-3), helper T cell 17 (Th17)/regulatory T cell (Treg) immune imbalance and pregnancy outcome in patients with unexplained recurrent spontaneous abortion (URSA). Methods: 62 cases of patients with URSA repregnancy who visited Hunan maternal and child health hospital from January 2020 to January 2022 were selected as the study group, and 30 normal early pregnant women who underwent pregnancy test during the same period were selected as the control group. The serum 1,25(OH) ₂D₃, sTim-3 and peripheral blood Th17 cell, Treg cell levels and the Th17/Treg ratio were compared in the two groups during early pregnancy. The correlations of serum 1,25(OH) ₂D₃ and sTim-3 and peripheral blood Th17 cell, Treg cell levels and Th17/Treg ratio were analyzed by Pearson method. According to the different pregnancy outcome of patients with URSA repregnancy, they were divided into successful pregnancy delivery group and pregnancy miscarriage group. The serum 1,25(OH) ₂D₃ and sTim-3, peripheral blood Th17 cell, Treg cell levels and Th17/Treg ratio were compared in the two groups during early pregnancy. The predictive value of serum 1,25(OH) ₂D₃, sTim-3, peripheral blood Th17 cell and Treg cell levels and Th17/Treg ratio in pregnancy outcome were analyzed by receiver operating characteristic (ROC) curve. Results: The serum sTim-3, peripheral blood Th17 cell levels and Th17/Treg ratio in the study group were higher than those in the control group, and the serum 1,25(OH) ₂D₃ and peripheral blood Treg cell levels were lower than those in the control group (P<0.05). Pearson correlation analysis showed that serum 1,25(OH) ₂D₃ was negatively correlated with serum sTim-3, peripheral blood Th17 cell levels and Th17/Treg ratio in patients with URSA repregnancy, and positively correlated with Treg cell level (P<0.05). Serum sTim-3 was negatively correlated with peripheral blood Treg cell level, and positively correlated with Th17 cell level and Th17/Treg ratio (P<0.05). The serum sTim-3, peripheral blood Th17 cell levels and Th17/Treg ratio in the pregnancy miscarriage group were higher than those in successful pregnancy delivery group, and the serum 1,25(OH) ₂D₃ and peripheral blood Treg cell levels were lower than those in the successful pregnancy delivery group (P<0.05). ROC curve analysis showed that serum 1,25(OH) ₂D₃, sTim-3, peripheral blood Th17 and Treg cell levels and Th17/Treg ratio could predict the risk of pregnancy loss again in patients with URSA repregnancy, and the combined detection of the above indexes had higher predictive efficacy. Conclusion: The abnormal decrease of serum 1,25(OH) ₂D₃ level and the abnormal increase of sTim-3 level can lead to Th17/Treg immune imbalance, leading to the recurrence of abortion in patients with URSA repregnancy. The combined detection of the above indexes is more effective in predicting the pregnancy loss again of patients with URSA repregnancy.