Identifying immune mechanisms mediating the hypertension during preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy-associated disorder that affects 5-8% of pregnancies and is a major cause of maternal, fetal, and neonatal morbidity and mortality. Hallmark characteristics of PE are new onset hypertension after 20 wk gestation with or without proteinuria, chronic immune activation, fetal growth restriction, and maternal endothelial dysfunction. However, the pathophysiological mechanisms that lead to the development of PE are poorly understood. Recent data from studies of both clinical and animal models demonstrate an imbalance in the subpopulations of CD4+ T cells and a role for these cells as mediators of inflammation and hypertension during pregnancy. Specifically, it has been proposed that the imbalance between two CD4+ T cell subtypes, regulatory T cells (Tregs) and T-helper 17 cells (Th17s), is involved in the pathophysiology of PE. Studies from our laboratory highlighting how this imbalance contributes to vasoactive factors, endothelial dysfunction, and hypertension during pregnancy will be discussed in this review. Therefore, the purpose of this review is to highlight hypertensive mechanisms stimulated by inflammatory factors in response to placental ischemia, thereby elucidating a role.

The impact of proteinuria on maternal and perinatal outcomes among women with pre‐eclampsia

“…Nonetheless, immunologic and inflammatory factors play important roles in the development of this disease, and the first contact between a women's immune systems and an abundance of nonself antigen that comes from the fetus could activate those factors. 12,13 The present study cohort had a high incidence of severe preeclampsia, which was diagnosed when clinical or laboratory findings suggested organ failure, imminent onset of eclampsia, or elevated blood pressure. The use of proteinuria as the selection criteria could, therefore, have led to bias as women with mild term pre-eclampsia often undergo delivery without assessment of a 24-hour urine sample.…”

“…The pathophysiologic mechanisms of pre‐eclampsia are unclear. Nonetheless, immunologic and inflammatory factors play important roles in the development of this disease, and the first contact between a women's immune systems and an abundance of non‐self antigen that comes from the fetus could activate those factors …”

Chronic infusion of interleukin‐17 promotes hypertension, activation of cytolytic natural killer cells, and vascular dysfunction in pregnant rats

“…; LaMarca et al. ). Our group has previously demonstrated that depletion of NK cells in the RUPP model improves both maternal and fetal outcomes (Elfarra et al.…”

“…; LaMarca et al. ; Taylor and Sasser ). In contrast to normal pregnancy, many studies have shown that NK cells in the decidua of preeclamptic women are composed of a higher cytolytic NK (cNK) cell population and a predominance of pro‐inflammatory T H 17 cells along with a corresponding decrease in T Reg number and function (Prins et al.…”

Increased serum levels of high mobility group protein B1 and calprotectin in pre‐eclampsia

“…Potential etiological factors for this complication of pregnancy include poor placentation, excessive maternal inflammation and immune response, and endothelial dysfunction . Several studies have reported that an exaggerated inflammatory response and an imbalanced immune response together play important roles in the development of pre‐eclampsia …”