Increasing evidence suggests that an exaggerated maternal systemic inflammatory response, as well as an angiogenic imbalance plays a central role in the pathogenesis of preeclampsia. In this study, we determined circulating levels of interleukin-17 (IL-17) along with those of angiogenic factors in healthy non-pregnant and pregnant women and preeclamptic patients, and examined whether serum IL-17 levels of preeclamptic patients were related to their clinical features and angiogenic factor concentrations. Fifty-nine preeclamptic patients, 60healthy pregnant women and 56 healthy non-pregnant women were involved in this casecontrol study. Serum levels of IL-17A were measured by high sensitivity ELISA. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and biologically active placental growth factor (PlGF) levels were determined by electrochemiluminescence immunoassay. For statistical analyses, non-parametric methods were applied. Serum IL-17 levels were significantly higher in preeclamptic patients than in healthy non-pregnant and pregnant women. We did not find any relationship between serum IL-17 concentrations of preeclamptic patients and their clinical features and serum sFlt-1 and PlGF levels or sFlt-1/PlGF ratios. However, elevated serum IL-17 level and sFlt-1/PlGF ratio was found to be additive for the risk of preeclampsia, as shown by the substantially higher odds ratios of their combination than of either alone. In conclusion, serum IL-17 levels are increased in preeclampsia, which might contribute to the development of the excessive systemic inflammatory response characteristic of the maternal syndrome of the disease. In addition, elevated serum IL-17 level and sFlt-1/PlGF ratio had an additive (joint) effect in the risk of preeclampsia.

SummaryFicolins 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 fmslike 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.

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An imbalance of maternal circulating pro- and anti-angiogenic factors may play a role in the pathogenesis of pre-eclampsia. Thrombospondin 2 (TSP-2) is a protein expressed mainly by activated endothelial cells, which acts as a potent anti-angiogenic agent. Our aim was to determine whether serum TSP-2 levels are altered in pre-eclampsia. We enrolled 35 pre-eclamptic patients and 35 healthy pregnant women in the study. Thrombospondin 2 levels were determined by enzyme-linked immunosorbent assay, while soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) concentrations were determined by electrochemiluminescence immunoassay. In patients with PE, we demonstrated 1.7-fold higher TSP-2 [13.2 (9.4-18.1) vs. 7.9 (7.2-11.2) ng/ml, p<0.001], 3.8-fold higher sFlt-1 and 4.3-fold lower PlGF levels compared with the control group. There were no associations between TSP-2 and sFlt-1 or PlGF concentrations. We suggest that circulating TSP-2 levels may contribute to the pathogenesis of PE via its anti-angiogenic properties, but in a distinct way from sFlt-1 and PlGF.

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