ABSTRACT
Preeclampsia (PE) is a leading cause of maternal and fetal mortality worldwide. The immune system plays a critical role in normal pregnancy progression;however, inappropriate inflammatory responses have been consistently linked with PE pathophysiology. This inflammatory phenotype consists of activation of the innate immune system, adaptive immune system, and increased inflammatory mediators in circulation. Moreover, recent studies have shown that the inflammatory profile seen in PE persists into the postpartum period. This manuscript aims to highlight recent advances in research relating to inflammation in PE as well as the inflammation that persists postpartum in women after a PE pregnancy. With the advent of the COVID-19 pandemic, there has been an increase in obstetric disorders associated with COVID-19 infection during pregnancy. This manuscript also aims to shed light on the relationship between COVID-19 infection during pregnancy and the increased incidence of PE in these women.
ABSTRACT
Preeclampsia (PE) is a leading cause of maternal and fetal mortality worldwide. The immune system plays a critical role in normal pregnancy progression; however, inappropriate inflammatory responses have been consistently linked with PE pathophysiology. This inflammatory phenotype consists of activation of the innate immune system, adaptive immune system, and increased inflammatory mediators in circulation. Moreover, recent studies have shown that the inflammatory profile seen in PE persists into the postpartum period. This manuscript aims to highlight recent advances in research relating to inflammation in PE as well as the inflammation that persists postpartum in women after a PE pregnancy. With the advent of the COVID-19 pandemic, there has been an increase in obstetric disorders associated with COVID-19 infection during pregnancy. This manuscript also aims to shed light on the relationship between COVID-19 infection during pregnancy and the increased incidence of PE in these women.
ABSTRACT
Preeclampsia (PE), new onset hypertension associated with placental ischemia during pregnancy, is associated with a pro‐inflammatory state characterized by increased T Helper cells and B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1‐AA). We have previously shown that adoptive transfer of CD4+T cells from PE women causes a PE‐like phenotype in immunodeficient (nude athymic) pregnant rats. Moreover, our lab has shown that depletion of B Cells or inhibition of AT1‐AA, a product of B cell activation, attenuates hypertension in various rat models of PE. Interestingly, AT1‐AA has been found in patients with COVID‐19 (CV) infection. An increase incidence of PE has been associated with a history (hx) of COVID‐19 infection during pregnancy. Collectively, this information suggests not only that B cells play an important role in the production of AT1‐AA in PE, but also a hx of COVID‐19 infection during pregnancy may result in AT1‐AA, thereby, contributing to increased risk for PE. Although it is known that B cells are the only producers of antibodies and therefore produce AT1‐AA, recent studies have touted that B cells don’t play a role in the hypertension in response to placental ischemia. Current studies have only investigated B cells in animal models of PE;yet, no studies have examined the effects of B cells from PE patients to cause hypertension during pregnancy. We hypothesize that B cells play an important role to cause hypertension and other features of PE during pregnancy and that B cells in COVID hx pregnant patients contribute to AT1‐AA in pregnancy. To test this hypothesis, B cells were isolated from the placentas of normal pregnant control (NP), PE, normotensive CV hx, or PE CV hx patients upon delivery. Isolated B cells were transferred i.p. into pregnant Nude Athymic rats at gestation (GD) 12. On GD18 carotid catheters were inserted. Blood pressure (MAP) was measured, pups were weighed, and tissues were collected on GD19. Recipients of placental PE B cells had increased MAP (115±3 mmHg, n=6) compared to recipients of placental NP B cells (100±6 mmHg, n=4, p<0.05). There were no changes in placental:fetal weight ratio associated with PE B cells (0.42±0.02;n=9) compared to recipients of NP B cells (0.40±0.01, n=6). Also, recipients of placental PE B cells had elevated activated Natural Killer cells in their placentas (33±14, n=3) compared to recipients of NP B cells (24±12, n=2). Recipients of placental CV Hx PE B cells had elevated MAP (107±7 mmHg, n=2) compared to recipients of placental CV Hx NP B cells (99±8 mmHg, n=3). Animals that received CV hx PE B cells had reduced placental efficiency (0.430, n=1) compared to recipients of CV hx Normotensive B cells (0.38±0.01, n=3). Collectively, this study demonstrates an important role for PE B cells to cause hypertension during pregnancy;and indicates that B cells contribute to a higher incidence of PE in women with a history of COVID‐19 infection during pregnancy.