(1190) Placental CD20+B Cells from Preeclamptic women contribute to Neurovascular Dysfunction in rat model of PE

Preeclampsia (PE), new-onset hypertension in pregnancy, is associated with immune activation, B cells secreting agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA), and neurological complications. We have shown AT1-AA to contribute to neurovascular dysfunction during pregnancy and we know that it is produced postpartum up to 7 years, suggesting a memory B cell immune response. Therefore, we hypothesize that CD20+ B cells cause hypertension and neurovascular dysfunction that allows for transmission of high blood pressure to the brain via AT1-AA.

Study Design:

Three hundred thousand placental CD20+ B Cells from normal pregnant (NP) or PE patients were isolated at delivery and injected i.p. into nude athymic rats on gestational day (GD) 12. Mini-osmotic pumps containing the AT1-AA inhibitor peptide, ‘n7AAc’, were inserted on GD14. Between GD14 and GD19 memory and learning were assessed with a Barnes maze.  On GD19, blood pressure (MAP) and cerebral blood flow (CBF) autoregulation were measured with laser doppler flowmetry (LDF). A one-way ANOVA was used for statistical analysis.

Results:

MAP increased in PE B cell recipients (123±2 mmHg, n=8) compared to NP recipients (106±3 mmHg, n=11). MAP was lowered with ‘n7AAc’ to 110±3 mmHg (n=6). AT1-AA activity was elevated with PE B cells to 14±2 ΔBPM, n=6 compared to NP recipients (2±1 ΔBPM, n=5) and ‘n7AAc’ treated PE recipients (1±2 ΔBPM, n=6). Baseline CBF was significantly higher in PE recipients (569±63 LDF, n=3) compared to NP recipients (252±13 LDF, n=3) or ‘n7AAc’ treated PE recipients (317±58 LDF, n=3). CBF autoregulation was improved in ‘n7AAc’ treated PE recipients (43±4% increased transmission, n=3) compared to PE recipients (66±10% increased transmission, n=3). Over five days, PE recipients were slower to escape the Barnes maze than NP B cell recipients or ‘n7AAc’ treated PE B cell recipients.

Conclusion:

CD20+ B cells from PE women contribute to hypertension, AT1-AA and neurovascular and cognitive dysfunction during pregnancy supporting a role for B cells producing AT1-AA in the pathophysiology of PE.