Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Obstetrics and Gynecology, Konyang University Hospital, Daejeon, Republic of Korea.
Am J Reprod Immunol. 2024 Nov;92(5):e70020. doi: 10.1111/aji.70020.
The imbalance in the Th17/Regulatory T (Treg) cell ratio is associated with recurrent pregnancy loss (RPL). This study aimed to determine a cut-off for the Th17/Treg cell ratio to predict pregnancy outcomes in RPL and evaluate the effectiveness of intravenous immunoglobulin (IVIG) based on this cut-off value.
This retrospective cohort study included 49 idiopathic RPL and 75 controls. The subgroups of IL-17 T cell to Foxp3 T cell ratios in peripheral blood were measured using flow cytometry. The cut-off values of Th17/Treg cell ratios were determined by the ROC curve to distinguish between RPL and controls. The IVIG treatment effectiveness in pregnancy outcome was compared between high- and low-ratio groups. Pearson correlation assessed the Th17/Treg cell ratio's relationship with NK cell cytotoxicity (NKC), NK cell percentage, and Th1/Th2 cell ratio.
Using the ROC curve, we identified six Th17/Treg cell ratio markers with diagnostic value, and the following two, CD3IL-17 T cell/CD3Foxp3 T cell ratio (sensitivity at 97%) and CD4IL-17 T cell/CD3Foxp3 T cell ratio (specificity at 93.61%), showed the highest statistical significance in diagnosing idiopathic RPL. Among the six diagnostic markers, in terms of predicting pregnancy outcomes with IVIG treatment, CD3IL-17 T cell/CD4Foxp3 T cell ratio was the most valuable prognostic marker. In RPL women with high CD3IL-17 T cell/CD4Foxp3 T cell ratio (≥ 1.096), the live birth rate (LBR) was improved with IVIG treatment. (IVIG treatment, 78.57% vs. no IVIG, 28.57%, p = 0.026). On the other hand, RPL women with low CD3IL-17 T cell/CD4Foxp3 T cell ratio did not demonstrate the effectiveness of IVIG (LBRs with IVIG treatment, 50.00% vs. no IVIG, 84.62%, p = 0.219). In a correlation study, the CD3IL-17 T cell/CD4Foxp3 T cell ratio was an independent prognostic marker, showing no correlation with NKC, NK cell percentage, and Th1/Th2 cell ratio.
The CD3IL-17 T/CD4Foxp3 T cell ratio may serve as a valuable marker for understanding the pathogenesis of RPL, predicting pregnancy outcomes, and selecting candidates for immunotherapy. Our study demonstrates that IVIG treatment can significantly improve LBR in women with a high CD3IL-17 T/CD4Foxp3 T ratio, offering a promising therapeutic approach for this challenging condition.
Th17/调节性 T（Treg）细胞比例失衡与复发性流产（RPL）有关。本研究旨在确定 Th17/Treg 细胞比例的截断值，以预测 RPL 的妊娠结局，并评估基于该截断值的静脉注射免疫球蛋白（IVIG）的有效性。
这项回顾性队列研究纳入了 49 例特发性 RPL 和 75 例对照。使用流式细胞术测量外周血中白细胞介素 17 T 细胞与 Foxp3 T 细胞比值的亚群。通过 ROC 曲线确定 Th17/Treg 细胞比值的截断值，以区分 RPL 和对照组。比较高比值组和低比值组中 IVIG 治疗对妊娠结局的影响。Pearson 相关性评估 Th17/Treg 细胞比值与自然杀伤细胞细胞毒性（NKC）、NK 细胞百分比和 Th1/Th2 细胞比值的关系。
使用 ROC 曲线，我们确定了具有诊断价值的 6 个 Th17/Treg 细胞比值标志物，其中 CD3IL-17 T 细胞/CD3Foxp3 T 细胞比值（敏感性为 97%）和 CD4IL-17 T 细胞/CD3Foxp3 T 细胞比值（特异性为 93.61%）在诊断特发性 RPL 方面具有最高的统计学意义。在 6 个诊断标志物中，就 IVIG 治疗的妊娠结局预测而言，CD3IL-17 T 细胞/CD4Foxp3 T 细胞比值是最有价值的预后标志物。在 CD3IL-17 T 细胞/CD4Foxp3 T 细胞比值较高（≥1.096）的 RPL 女性中，IVIG 治疗可提高活产率（LBR）。（IVIG 治疗，78.57% vs. 无 IVIG，28.57%，p=0.026）。另一方面，CD3IL-17 T 细胞/CD4Foxp3 T 细胞比值较低的 RPL 女性未显示出 IVIG 的有效性（IVIG 治疗的 LBR 为 50.00% vs. 无 IVIG 的 84.62%，p=0.219）。在相关性研究中，CD3IL-17 T 细胞/CD4Foxp3 T 细胞比值是一个独立的预后标志物，与 NKC、NK 细胞百分比和 Th1/Th2 细胞比值无关。
CD3IL-17 T/CD4Foxp3 T 细胞比值可能是理解 RPL 发病机制、预测妊娠结局和选择免疫治疗候选者的有价值的标志物。我们的研究表明，IVIG 治疗可显著提高 CD3IL-17 T/CD4Foxp3 T 比值较高的女性的活产率，为这一具有挑战性的疾病提供了一种有前景的治疗方法。
