PL108. Inflammatory mechanisms in preeclampsia

Abstract

Introduction Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response. Objectives Our aim was to determine cellular and humoral components of the innate and adaptive immune system in normal pregnancy and preeclampsia. Methods In our case-control studies, we used flow cytometry, multiplex suspension array, ELISA, immunoturbidimetry and radial immunodiffusion for our measurements. Results High-throughput multiplex cytokine measurements demonstrate an overall pro-inflammatory systemic environment in preeclampsia with elevated amounts of pro-inflammatory cytokines, chemokines and adhesion molecules in the maternal circulation. In addition, circulating levels of positive acute phase proteins increase, whereas those of negative acute phase proteins decrease in preeclampsia, indicating an acute phase response. The complement system is activated systematically with increased terminal complex formation, as shown by the elevated amounts of activation markers in the systemic circulation. All three complement pathways (the classical, lectin and alternative) are involved in the excessive complement activation in preeclampsia. Regulatory T cells (Tregs) play an important role in the development of pregnancy-specific immune tolerance. The frequency of conventional CD4+ CD25high FoxP3+ and non-conventional CD4+ CD25− FoxP3+ Tregs is lower in preeclampsia, suggesting inadequate induction of tolerance to paternal antigens. The prevalence of the functionally most active effector Tregs is decreased, while that of exhausted Tregs is increased in preeclampsia. The combination of lower effector Treg and higher exhausted Treg prevalence may account for the decrease in the functionality of Tregs in preeclampsia. There is a shift not only in the Th1/Th2, but also in the Th17/Treg balance favouring skewness towards a pro-inflammatory status in preeclampsia. The prevalence of IL-17-producing CD8 (Tc17) and NK cells is also elevated in this pregnancy-specific disorder. Conclusion Our results indicate that both the innate and adaptive arms of the immune system are involved in the development of the exaggerated maternal systemic inflammation observed in preeclampsia.