Higher Circulating Lymphocytes and Incidence of Pre-eclampsia and Eclampsia
Pre-eclampsia and eclampsia are two of the most serious
acute multisystemic disorders during pregnancy and are significant determinants
of maternal and neonatal mortality on a global scale. Pre-eclampsia is
associated with an elevated susceptibility to adverse pregnancy outcomes, such
as preterm birth and intrauterine growth restriction, thereby amplifying the
risk of low birth weight. Furthermore, it is intricately linked to serious
maternal and neonatal health complications, including chronic hypertension,
maternal end-stage renal disease, and neonatal pulmonary dysplasia. The precise
etiology of pre-eclampsia remains elusive, although our current understanding
suggests that women afflicted with pre-eclampsia exhibit increased uterine
artery resistance due to impaired immune regulation. This, in turn, contributes
to the activation of the maternal endothelium and the onset of systemic chronic
inflammation. Multiple studies have found that immune cells change
significantly in women with pre-eclampsia.
Mendelian randomization (MR) presents a robust means to
investigate the causal relationship between immune cells and pre-eclampsia by
genetic variants (single nucleotide polymorphisms (SNPs)), and it is also less
susceptible to the shortcomings of classical epidemiological studies, such as
confounding bias, information bias, and selection bias. Recently, the
application of MR has gained significant traction in elucidating the causal
link between immune cells and various diseases such as hypertension, amyotrophic
lateral sclerosis and multiple sclerosis. In this study, authors utilized MR
and colocalization analysis to investigate the potential causal association
between immune cells and pre-eclampsia.
For exposure, authors extracted genetic variants associated
with immune cell-related traits, and for outcomes, they used summary genetic
data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR)
analysis was then performed to assess the causal relationship.
Study found that genetically proxied circulating lymphocyte
absolute count was causally associated with total eclampsia (odds ratio OR = 1
53, 95% confidence interval (CI) (1.31-1.79), p = 1 15E − 07) and pre-eclampsia
(OR = 1 50, 95% CI (1.28-1.77), p = 9 18E − 07); T cell absolute count was
causally associated with total eclampsia (OR = 1 49, 95% CI (1.28-1.73), p = 2
73E − 07) and pre-eclampsia (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 (OR = 1 83, 95% CI (1.44-2.32), p = 7 11E − 07) and pre-eclampsia (OR
= 1 77, 95% CI (1.38-2.26), p = 6 55E − 06).
Study findings collectively demonstrate significant
associations between genetically predicted lymphocyte and T cell count and the
risk of pre-eclampsia, as well as the combined occurrence of pre-eclampsia and
eclampsia. A complex interplay of acquired, genetic, and immune risk factors
collectively contributes to the onset of early placental dysfunction, and many
researchers believe that an abnormal maternal immune response to the fetus is the
initiating factor in the development of eclampsia. Moreover, this process
involves cells of the innate and adaptive immune systems, including
neutrophils, monocytes, natural killer (NK) cells, and T lymphocytes. This
dysfunction also triggers the release of antiangiogenic factors ultimately
culminating in subsequent multiorgan dysfunction.
This study demonstrated a causal relationship between
lymphocyte and T cell count and pre-eclampsia and the combination of
pre-eclampsia and eclampsia. Based on these findings, authors suggest that
routine blood examinations should be incorporated into the clinical evaluation
of pregnant woman more frequently. In addition, lymphocyte and T cell counts
should be monitored in patients with pre-eclampsia and eclampsia. However, additional
investigations are imperative to corroborate and validate these findings, in
order to evaluate their robustness and generalizability.
Source: Qiuping Zhao, Rongmei Liu, Hui Chen; Hindawi Journal
of Pregnancy Volume 2024, Article ID 8834312, 7 pages https://doi.org/10.1155/2024/8834312
