Circulating ficolin-2 and ficolin-3 in normal pregnancy and pre-eclampsia.

Ficolins are soluble molecules of the innate immune system that recognize carbohydrate molecules on microbial pathogens, apoptotic and necrotic cells. They act through two distinct routes: initiating the lectin pathway of complement activation and mediating a primitive opsonophagocytosis. In this study, we measured plasma levels of ficolin-2 and ficolin-3 in 60 pre-eclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women by enzyme-linked immunosorbent assay (ELISA). Circulating levels of complement activation products (C4d, C3a, SC5b9), angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor) and markers of endothelial activation (von Willebrand factor antigen), endothelial injury (fibronectin) and trophoblast debris (cell-free fetal DNA) were also determined. Plasma levels of ficolin-2 were significantly lower in healthy pregnant than in healthy non-pregnant women, while ficolin-3 levels did not differ significantly between the two groups. Furthermore, pre-eclamptic patients had significantly lower ficolin-2 and ficolin-3 concentrations than healthy non-pregnant and pregnant women. In the pre-eclamptic group, plasma ficolin-2 levels showed a significant positive correlation with serum placental growth factor (PlGF) concentrations and significant inverse correlations with serum levels of soluble fms-like tyrosine kinase-1 (sFlt-1), blood urea nitrogen and creatinine, serum lactate dehydrogenase activities, as well as with plasma VWF:antigen, fibronectin and cell-free fetal DNA concentrations. In conclusion, circulating levels of ficolin-2 are decreased in the third trimester of normal pregnancy. There is a further decrease in plasma ficolin-2 concentrations in pre-eclampsia, which might contribute to the development of the maternal syndrome of the disease through impaired removal of the trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed pre-eclamptic placenta.

OS004. A link between the complement system and angiogenic imbalance inpreeclampsia: ficolin-2 deficiency.

INTRODUCTION: An excessive maternal systemic inflammatory response to pregnancy, as well as an imbalance between circulating angiogenic factors and their antagonists plays a central role in the pathogenesis of preeclampsia. The complement system, as part of innate immunity, is fundamental to the host's immune defense against microbial pathogens, apoptotic and necrotic cells. Both of its excessive activation and deficiencies can lead to various disorders. OBJECTIVES: The aim of this study was to determine circulating levels of components of the complement system and their relationship to those of angiogenic factors in normal pregnancy and preeclampsia. METHODS: Sixty preeclamptic patients, 60 healthy pregnant women and 59 healthy non-pregnant women were involved in this case-control study. Circulating levels of C1rC1sC1-inh, C3bBbP, C4d, C3a, SC5b9, ficolin-2, ficolin-3, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), as well as activity of the complex of mannose-binding lectin and mannose-binding lectin-associated serine protease 2 (MBL-MASP2 complex) were measured. For statistical analyses, non-parametric methods were applied. RESULTS: Circulating levels of C3bBbP, C4d, C3a, SC5b9, sFlt-1, PlGF, as well as MBL-MASP2 activity were significantly higher, while ficolin-2 concentrations were significantly lower in healthy pregnant than in healthy non-pregnant women. Furthermore, preeclamptic patients had significantly higher C1rC1sC1-inh, C3bBbP, C4d, C3a, SC5b9 and sFlt-1 levels and significantly lower ficolin-2, ficolin-3 and PlGF concentrations than healthy pregnant women. In the groups of healthy pregnant women and preeclamptic patients, plasma ficolin-2 levels showed a significant positive correlation with serum PlGF concentrations and a significant inverse correlation with serum levels of sFlt-1. There was no other relationship between complement components and angiogenic factors in either study group. CONCLUSION: Elevated levels of activation products in the systemic circulation indicate complement activation with increased terminal complex formation in preeclampsia, which seems to be independent from alterations in circulating angiogenic factors. Nevertheless, low ficolin-2 concentrations might contribute to the angiogenic imbalance in preeclampsia by impaired removal of the sFlt-1-containing trophoblast-derived material released into the maternal circulation by the hypoxic and oxidatively stressed preeclamptic placenta.