Abstract 018: B Cells Induce Hypertension, AT1AA, And Complement Activation In Preeclampsia Or In Response To A Prior Covid-19 Infection During Pregnancy

Abstract

Preeclampsia (PE), new onset hypertension (HTN) during pregnancy, is associated with placental ischemia and chronic inflammation that includes increased CD4+ T cells, B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1AA), and activation of the complement system. Previous studies have shown AT1-AA is produced in patients with COVID-19 infection. Interestingly, having had COVID-19 during pregnancy is associated with increased incidence of developing a PE phenotype during pregnancy. We have previously shown an important role for B cell depletion or AT1AA inhibition to attenuate HTN in rat models of PE. Collectively, this data suggests B cells contribute to PE development and that B cells may increase incidence of PE in patients with a history (Hx) of COVID-19 during pregnancy through production of the AT1AA. We hypothesize B cells from PE or CV Hx PE patients produce AT1AA resulting in HTN and complement activation in pregnancy. Placental B cells were isolated from normal pregnant (NP), PE, normotensive (NT) CV Hx, or PE CV Hx patients at delivery. B cells were transferred i.p. into pregnant athymic rats at gestation (GD) 12. On GD18, carotid catheters were inserted. On GD19, blood pressure was measured and tissues collected. PE B cell recipients had increased Mean Arterial Pressure (MAP) (115±3 mmHg n=6) compared to NP B cell recipients (97±4 mmHg n=6 p<0.05). PE B cell recipients had increased AT1AA (20±2 ΔBPM n=4) compared to NP B cell recipients (6±1 ΔBPM n=4 p<0.05). PE B cell recipients had increased markers of complement activation such as reduced plasma C4 (1302±169 μg/mL n=4) and C3 (516±45 μg/mL n=4) compared to recipients of NP B cells (2348±338 μg/mL n=4 p<0.05) and (790±66 μg/mL n=4 p<0.05) respectively. CV Hx PE B cell recipients had elevated MAP (108±3 mmHg n=4) compared to CV Hx NT B cell recipients (101±7 mmHg n=4) and increased AT1AA (24±3 ΔBPM n=3) compared to CV Hx NT B cell Recipients (4±1 ΔBPM n=4 p<0.05). Collectively, this study demonstrates an important role for B cells to cause HTN during pregnancy; and indicates that B cells contribute to a higher incidence of PE in women with a Hx of CV infection during pregnancy possibly by secreting AT1-AA.