A leading role for the immune system in the pathophysiology of preeclampsia

Abstract

Preeclampsia syndrome is characterized by inadequate placentation, because of deficient trophoblastic invasion of the uterine spiral arteries, leading to placental hypoxia, secretion of proinflammatory cytokines, the release of angiogenic and antiangiogenic factors and miRNAs. Although immune-system alterations are associated with the origin of preeclampsia, other factors, including proinflammatory cytokines, neutrophil activation, and endothelial dysfunction, are also related to the pathophysiology of this syndrome. The pathophysiology of preeclampsia may involve several factors, including persistent hypoxia at the placental level and the release of high amounts of STBMs. DAMP molecules released under hypoxic conditions and STBMs, which bind TLRs, may activate monocytes, DCs, NK cells, and neutrophils, promoting persistent inflammatory conditions in this syndrome. The development of hypertension in preeclamptic women is also associated with endothelial dysfunction, which may be mediated by various mechanisms, including neutrophil activation and NET formation. Furthermore, preeclamptic women have higher levels of nonclassic and intermediate monocytes and lower levels of lymphoid BDCA-2(+) DCs. The cytokines secreted by these cells may contribute to the inflammatory process and to changes in adaptive-immune system cells, which are also modulated in preeclampsia. The changes in T cell subsets that may be seen in preeclampsia include low Treg activity, a shift toward Th1 responses, and the presence of Th17 lymphocytes. B cells can participate in the pathophysiology of preeclampsia by producing autoantibodies against adrenoreceptors and autoantibodies that bind the AT1-R.

Sterile inflammation and pregnancy complications: a review

“…This localized oxygen and nutrient deprivation is associated with exaggerated trophoblast cell death (Jones & Fox 1980, Chua et al 1991, Knight et al 1998, Johansen et al 1999, Leung et al 2001, which has been suggested to directly contribute to the disease by releasing mediators of inflammation that promote endothelial activation and systemic maternal inflammation (Smarason et al 1993, Knight et al 1998, Redman & Sargent 2003. Although the etiology of PE is mostly unknown, a major hallmark is a generalized inflammatory response characterized by high cytokine levels, such as IL-1β, IL-6, IL-8 and tumor necrosis factor-α (Vince et al 1995, Mellembakken et al 2001, Laresgoiti-Servitje 2013, Harmon et al 2016. Because this inflammatory response usually occurs in the absence of microbial infection, PE primarily represents a sterile inflammation.…”

Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy

“…Although the vascular alterations occurring in pre-eclampsia are well established (43), the impact of immune components in its pathogenesis is less clear (7). Thus, we next interrogated the role of neutrophils in niT-cell induction in women with preeclampsia.…”

“…Immune tolerance of the fetus relies on the concerted actions of hormones and cytokines, as well as cross-talk between innate and adaptive immune cells (6). Dysregulation of one or more of these components can lead to complications of pregnancy, including fetal growth restriction, preeclampsia, and recurrent miscarriages (7).…”

Iodine levels are associated with oxidative stress and antioxidant status in pregnant women with hypertensive disease

“…Although there have been great advances in medicine, the frequency of this disease has not been successfully modified significantly (3). Currently, the etiology of this disease remains unknown, therefore, in order to explain its origin various theories have been raised, and within each of them the genetic origin, immune factor, endothelial dysfunction, increased oxidative stress, micronutrients deficiency, among others, can be mentioned (3)(4)(5)(6)(7)(8). During pregnancy, there is a normal increase in the production of reactive oxygen species (ROS); likewise, the antioxidant capacity is increased.…”