Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, China; Laboratory of Reproductive and Stem Cell Engineering, Key Laboratory of National Health and Family Planning Commission, Changsha, Hunan 410078, China.
Institute of Reproductive & Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, Hunan 410008, China; Clinical Research Center for Reproduction and Genetics in Hunan Province, Reproductive & Genetic Hospital of CITIC-XIANGYA, Changsha, Hunan 410008, China; Laboratory of Reproductive and Stem Cell Engineering, Key Laboratory of National Health and Family Planning Commission, Changsha, Hunan 410078, China.
Int Immunopharmacol. 2022 Sep;110:108960. doi: 10.1016/j.intimp.2022.108960. Epub 2022 Jun 24.
The aim of this study was to investigate the relationship between pre-pregnancy blood immune status and unexplained recurrent pregnancy loss (URPL), and to evaluate the predictive value of pre-pregnancy blood Treg levels for subsequent miscarriage in patients with URPL. We retrospectively analyzed 76 women who had experienced two or more miscarriages before 24 weeks of gestation for no obvious reason, and 74 women who had achieved live births as controls. Flow-cytometric analysis of peripheral blood CD4 + T cells, CD8 + T cells, NK cells, NKT cells, B cells, NK cell subpopulations (including CD56 NK cells, CD56 NK cells, CD56CD16 NK cells, and CD56CD16 NK cells) was executed in the luteal phase of women in the URPL and control groups. When we reviewed and analyzed reproductive outcomes in URPL patients, we found that blood Tregs were significantly lower in the URPL group than in the controls (1.89% ± 0.61% vs. 2.15% ± 0.58%, P < 0.01) during the luteal phase pre-pregnancy. However, we discerned no differences among blood CD4T cells, CD8T cells, B cells, NKT cells, or NK cells, NK subpopulations (CD56 NKs, CD56 NKs, CD56CD16 NKs, or CD56CD16 NKs) between the two groups. By implementing receiver operating characteristic (ROC) curve analysis to determine whether Treg levels predicted subsequent miscarriages, we found that the area under the ROC curves was 0.714, and that the cutoff value was 1.35, with a sensitivity of 0.556 and specificity of 0.923. Based on the cutoff value, we divided pregnant URPL patients into two groups, demonstrating that the subsequent miscarriage rates in the low-Treg level group (<1.35%) were significantly higher than those in the normal-Treg level group (>1.35%) (71.43% vs. 14.29%, P < 0.01). CONCLUSION: The pre-pregnancy blood Treg level was a potential marker that predicted subsequent miscarriage in women with URPL.
本研究旨在探讨孕前血液免疫状态与不明原因复发性妊娠丢失（URPL）之间的关系，并评估孕前 Treg 水平对 URPL 患者随后流产的预测价值。我们回顾性分析了 76 例因不明原因在 24 周前发生两次或两次以上流产的患者（URPL 组）和 74 例成功分娩的患者（对照组）。采用流式细胞术分析 URPL 组和对照组患者黄体期外周血 CD4+T 细胞、CD8+T 细胞、NK 细胞、NKT 细胞、B 细胞、NK 细胞亚群（包括 CD56+NK 细胞、CD56+NK 细胞、CD56+CD16+NK 细胞和 CD56+CD16+NK 细胞）。当我们回顾和分析 URPL 患者的生殖结局时，发现 URPL 组患者孕前黄体期血液 Treg 明显低于对照组（1.89%±0.61%比 2.15%±0.58%，P<0.01）。然而，两组间血液 CD4T 细胞、CD8T 细胞、B 细胞、NKT 细胞或 NK 细胞、NK 细胞亚群（CD56+NK 细胞、CD56+NK 细胞、CD56+CD16+NK 细胞或 CD56+CD16+NK 细胞）无差异。通过实施受试者工作特征（ROC）曲线分析来确定 Treg 水平是否预测随后的流产，我们发现 ROC 曲线下面积为 0.714，截断值为 1.35，灵敏度为 0.556，特异性为 0.923。基于截断值，我们将 URPL 孕妇分为两组，结果显示低 Treg 水平组（<1.35%）的随后流产率明显高于正常 Treg 水平组（>1.35%）（71.43%比 14.29%，P<0.01）。结论：孕前血液 Treg 水平是预测 URPL 患者随后流产的一个潜在标志物。
