Wang Yuxiu, Ni Shijun, Liu Feng, Guo Lining, Han Cha
Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin, China; Tianjin Key Laboratory of Female Reproductive Health and Eugenics, Tianjin Medical University General Hospital, Tianjin, China.
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin, China.
J Reprod Immunol. 2025 Mar;168:104428. doi: 10.1016/j.jri.2025.104428. Epub 2025 Jan 15.
Preeclampsia (PE) is a complex hypertensive disorder that occurs during pregnancy, with the immune system playing a key role. Although immune modulation is implicated in PE progression, the roles of specific immune cells and inflammatory mediators remain unclear.
We conducted a two-sample, two-step Mendelian randomization (MR) analysis, primarily using the inverse-variance weighted method, to investigate the causal effect of immune cell traits on PE. Additionally, we assessed the potential mediation effects of inflammatory factors.
The MR analyses revealed that 22 immune cell traits exert protective effects against PE, whereas 19 are associated with an increased risk. Additionally, four inflammatory factors were suggested to be linked to PE. Mediation analysis identified the absolute count (AC) of CD33 + HLA DR+ cells, including the CD14 - subset, as causally related to PE. Both the total effect of the CD33 + HLA DR+ AC (odds ratio [OR] = 0.977, 95 % confidence interval [CI], 0.960-0.994; P = 0.010) and the effect of CD33 + HLA DR+ CD14 - cells (OR = 0.977, 95 % CI, 0.963-0.991; P = 0.001) were significant. These effects were partially mediated by STAM-binding protein levels, contributing 16.7 % and 15.0 % to the total effects of the CD33 + HLA DR+ AC and CD33 + HLA DR+ CD14 - AC, respectively.
This study establishes a causal relationship between specific immune cells and PE, potentially mediated by inflammatory factors, highlighting the importance of these traits in PE pathogenesis. Further research is needed to validate these findings based on larger, more diverse cohorts.
子痫前期（PE）是一种在孕期发生的复杂高血压疾病，免疫系统在其中起关键作用。尽管免疫调节与PE的进展有关，但特定免疫细胞和炎症介质的作用仍不清楚。
我们进行了一项两样本、两步孟德尔随机化（MR）分析，主要使用逆方差加权法，以研究免疫细胞特征对PE的因果效应。此外，我们评估了炎症因子的潜在中介作用。
MR分析显示，22种免疫细胞特征对PE有保护作用，而19种与风险增加有关。此外，有四种炎症因子被认为与PE有关。中介分析确定CD33 + HLA DR +细胞（包括CD14 -亚群）的绝对计数（AC）与PE存在因果关系。CD33 + HLA DR + AC的总效应（优势比[OR]=0.977，95%置信区间[CI]，0.960 - 0.994；P = 0.010）和CD33 + HLA DR + CD14 -细胞的效应（OR = 0.977，95% CI，0.963 - 0.991；P = 0.001）均具有统计学意义。这些效应部分由STAM结合蛋白水平介导，分别占CD33 + HLA DR + AC和CD33 + HLA DR + CD14 - AC总效应的16.7%和15.0%。
本研究建立了特定免疫细胞与PE之间的因果关系，可能由炎症因子介导，突出了这些特征在PE发病机制中的重要性。需要进一步的研究基于更大、更多样化的队列来验证这些发现。
