Role of the CD40–CD40L expression level pathway in the diagnosis of unexplained recurrent pregnancy loss

Unexplained recurrent spontaneous pregnancy loss (URPL) lacks effective treatment and reliable early diagnosis and prediction. Immunologic dysfunction can be an underlying cause of recurrent pregnancy loss (RPL). Considering the regulatory role of CD40–CD40L in immune responses, we explored its clinical significance in URPL. The 108 women with URPL who were treated in Hebei Yanda Hospital from January 2020 to December 2022 were selected as study subjects, and another 108 healthy women who were not pregnant and matched with the age and body mass index of the study group were selected as the control group. CD40 and CD4 + CD25 + Treg cells in peripheral blood mononuclear cells (PBMCs) and CD40L in peripheral blood platelets were measured by flow cytometry. The predictive value of CD40–CD40L in URPL for the risk of RPL was determined by receiver operating characteristic (ROC) curves. The correlations of CD40–CD40L with CD4 + CD25 + Treg cells and serum pro-inflammatory factors were assessed by Pearson’s analysis. CD40 on the surface of PBMCs and CD40L on the surface of platelets were up-regulated in URPL patients. CD40 in combination with CD40L had high predictive value for the risk of RPL in URPL patients. Peripheral blood CD40–CD40L was positively linked to IL-17 and IL-23, and negatively to CD4 + CD25 + Treg cells and IL-10 in URPL patients. The CD40–CD40L pathway expression in peripheral blood can help predict the risk of RPL in URPL patients. This study discovered significant increases in the blood levels of two transmembrane glycoproteins, CD40 and CD40L, in patients with two or more consecutive unexplained recurrent spontaneous pregnancy loss, compared to healthy women. The elevated levels of CD40 and CD40L indicated an increased risk of recurrent pregnancy loss in these patients, which could help early and timely management of these patients.

不明原因复发性自然流产（Unexplained recurrent spontaneous pregnancy loss, URPL）目前尚无有效的治疗手段与可靠的早期诊断及预测方法。免疫功能异常可作为复发性流产（recurrent pregnancy loss, RPL）的潜在病因。鉴于CD40–CD40L在免疫应答中的调控作用，本研究探讨了其在URPL中的临床意义。本研究选取2020年1月至2022年12月于河北燕达医院就诊的108例URPL患者作为研究对象，另选取108例未妊娠、年龄与体质量指数与研究组匹配的健康女性作为对照组。采用流式细胞术检测外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）表面的CD40、CD4+CD25+调节性T细胞以及外周血血小板表面的CD40L表达水平；通过受试者工作特征（receiver operating characteristic, ROC）曲线分析CD40–CD40L对URPL患者复发性流产风险的预测价值；采用Pearson相关分析评估CD40–CD40L与CD4+CD25+调节性T细胞及血清促炎因子的相关性。研究结果显示，URPL患者外周血单个核细胞表面的CD40与血小板表面的CD40L表达均显著上调；CD40联合CD40L对URPL患者的复发性流产风险具有较高的预测价值；URPL患者外周血CD40–CD40L通路与IL-17、IL-23呈正相关，与CD4+CD25+调节性T细胞及IL-10呈负相关。外周血CD40–CD40L通路的表达水平可辅助预测URPL患者的复发性流产风险。本研究发现，相较于健康女性，连续发生2次及以上不明原因复发性自然流产的患者，其血液中两种跨膜糖蛋白CD40与CD40L的水平显著升高；CD40与CD40L的水平升高提示此类患者的复发性流产风险增加，可为该类患者的早期及时干预提供临床参考。