Distinct DNA Methylation Signatures in Maternal Blood Reveal Unique Immune Cell Shifts in Preeclampsia and the Pregnancy-Postpartum Transition

Abstract

1.0Preeclampsia (PE) is a hypertensive disorder of pregnancy characterized by immune dysregulation and significant risks to maternal and fetal health. While current management relies on high-risk patient monitoring and early diagnosis, these methods are costly and burdensome, especially for low-risk pregnancies. There is a pressing need for non-invasive tools to predict and monitor PE. DNA methylation (DNAm) is a type of DNA modification that influences gene expression, and has been associated with immune cell dynamics and PE pathogenesis. This study explores whether DNAm-based immune cell composition profiling can provide insights into PE-related immune dysregulation. We conducted a search in the Gene Expression Omnibus (GEO) for DNA methylation datasets using Illumina 27K, 450K, and EPIC arrays from maternal blood in both healthy and PE pregnancies. We found two studies that met our criteria, involving a total of 24 healthy pregnancies and 14 with PE. To estimate the composition of immune cells (including CD8T, CD4T, Monocytes, Natural Killer, Neutrophils, Eosinophils, and B cells) based on DNA methylation data, we employed the R package EpiDISH. We used a linear model to compare statistical differences in the proportions of immune cells between PE cases and the control group. Longitudinal trends were also examined to capture immune cell shifts from pregnancy to postpartum. We found that monocyte proportions were significantly reduced in preeclamptic pregnancies compared to normotensive pregnancies (p=0.013). No significant differences were observed in other immune cell types, including T cells, B cells, neutrophils, eosinophils, and natural killer cells. Longitudinal analyses revealed substantial immune cell shifts in the postpartum period, including increased monocytes, B cells, CD4+ T cells, and CD8+ T cells, emphasizing the importance of gestational age in immune dynamics. These findings support DNAm profiling as a valuable tool for understanding immune cell dynamics in PE. Reduced monocyte proportions in PE highlight the role of immune dysregulation in its pathogenesis. Longitudinal sampling provides additional insights into the evolution of immune changes throughout pregnancy and postpartum, offering potential for developing predictive and monitoring tools for PE. Future studies with larger, more diverse cohorts are essential to refine the utility of DNAm in pregnancy complications.