Association between cellular immune and preeclampsia and preterm birth: A Mendelian randomization study

Abstract

Emerging evidences have highlighted immune-inflammatory imbalances as a critical driver of the pathogenesis for preeclampsia (PE) and preterm birth (PB), but the impact of specific immune factors on the diseases is largely unknown. Our aim was to determine whether these immune cells are causally associated with the onset of PE or PB. Drawing on publicly available genetic data, we applied Mendelian randomization analysis to probe the causal link of 731 immune traits (7 panels: TBNK panel, Regulatory T cells panel, Maturation stages of T-cell panel, Dendritic cell panel, B-cell panel, Monocyte panel and Myeloid cell pane) with the risk of PE and PB. The inverse variance weighting method (IVW) acted as the primary analysis to estimate the validity of causality, and sensitivity analyses were conducted to assessment of heterogeneity and pleiotropy. After adjusting for P-values for FDR method, CD27 on CD24+ CD27+ B cell, CD80 on plasmacytoid Dendritic Cell, CD33+ HLA DR+ CD14dim Absolute Count, CD33+ HLA DR+ CD14- Absolute Count, CD33+ HLA DR+ Absolute Count were remarkably causally involved in increased risk of PE, while HLA DR on Dendritic Cell exerted a protective causation against PE (P_FDR < 0.05). Moreover, we determined that CD45 on CD33dim HLA DR- in myeloid cells decreased PB risk, whereas CD11b on Granulocytic Myeloid-Derived Suppressor Cells had the opposite effect on PB (F_FDR < 0.2). This study provided genetic evidence for causal relationships between immune cell traits and PE and PB, offering potential candidate immunophenotypes for future studies on the etiology of pregnancy complications.