Causal relationships between immune cells, inflammatory factors, and preeclampsia: A two-step, two-sample mendelian randomization study

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.