Study demonstrates causal relationship between lymphocyte and T cell count with 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
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