Higher Circulating Lymphocytes and the Incidence of Pre-eclampsia and Eclampsia

Abstract

Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia ($\text{odds}\text{ratio}\left(\text{OR}\right)=1.53$, 95% confidence interval (CI) (1.31-1.79), $p=1.15E-07$) and pre-eclampsia ($\text{OR}=1.50$, 95% CI (1.28-1.77), $p=9.18E-07$); T cell absolute count was causally associated with total eclampsia ($\text{OR}=1.49$, 95% CI (1.28-1.73), $p=2.73E-07$) and pre-eclampsia ($\text{OR}=1.47$, 95% CI (1.25-1.72), $p=1.76E-06$). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia ($\text{OR}=1.83$, 95% CI (1.44-2.32), $p=7.11E-07$) and pre-eclampsia ($\text{OR}=1.77$, 95% CI (1.38-2.26), $p=6.55E-06$). Colocalization analysis revealed that immune cell-related traits shared the same variant with pre-eclampsia/eclampsia. Our study suggested causal effects of genetic predisposition to high lymphocyte absolute count levels, T cell absolute count, and CD28- CD25+ CD8+ T cell absolute count on eclampsia, particularly pre-eclampsia risk, providing crucial new insights into the potential prevention target for eclampsia and pre-eclampsia.