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

Abstract

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.

Early second-trimester plasma protein profiling using multiplexed isobaric tandem mass tag (TMT) labeling predicts gestational diabetes mellitus

“…Ficolin-3 binds to GlcNAc, Nacetyl-galactosamine (GalNAc) and fucose [39]. Preeclamptic patients had significantly lower ficolin-2 and ficolin-3 concentrations than healthy non-pregnant and pregnant women [40]. Recently, research showed that plasma ficolin-3, a kind of soluble PRR within the lectin pathway varied significantly between individuals with NGT and those with T2DM [41].…”

Commercially Available Complement Component-Depleted Sera Are Unexpectedly Codepleted of Ficolin-2

“…Ficolin-2 has been recently shown to be important during pneumococcal pathogenesis (2)(3)(4) and is known to bind to many other significant human pathogens (2,5,6). Moreover, ficolin-2 and -3 have been implicated in many different disease pathologies, such as transplant reperfusion injury (7), clearance of apoptotic cells (8,9), and even preeclampsia (10).…”

Blood Collection Tubes Influence Serum Ficolin-1 and Ficolin-2 Levels

“…Crystallography studies have shown that ficolin-1 and ficolin-3 have only one binding pocket each, while ficolin-2 has four binding pockets, which may make it a more promiscuous binder (4). Ficolin-2 is known to bind many acetylated ligands (5) and various biological ligands, such as apoptotic cells (6), and may be important in renal transplantation (7) and preeclampsia (8). It also binds to several significant human pathogens, like group B streptococcus (9) and Salmonella enterica serovar Typhimurium (10), and to many Gram-positive bacterial teichoic acids (11).…”