No abstract

Our results indicate that the frequency of conventional and non-conventional Tregs alters simultaneously, and the presence in circulation of both of these Treg subsets is similarly important in the adequate development of pregnancy-specific immune tolerance.

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.

Fas-mediated apoptosis of maternal lymphocytes during pregnancy has been postulated to prevent the development of pre-eclampsia. A single adenine (A) to guanine (G) polymorphism at position -670 in the Fas gene (TNFRSF6) results in decreased Fas synthesis. The association between this polymorphism and pre-eclampsia in Hungarian women was investigated. In a case-control study, buccal swabs from 38 pregnant women with pre-eclampsia and 89 normotensive controls were analysed for the TNFRSF6-670 polymorphism. Investigators were blinded to clinical outcomes. Maternal homozygosity for the TNFRSF6-670*A occurred in 33 (37.1%) normotensive pregnant women as compared to only 5 (16.1%) of 31 pre-eclamptic pregnant women who delivered at < 37 weeks gestation (P = 0.04). The carriage rate of the TNFRSF6-670*G variant was also higher among these patients (59.7%) than among normotensive controls (42.1%; P = 0.01). There was no relation between the polymorphism and the pre-eclampsia diagnosed at > or = 37 weeks. Among pre-eclamptic patients with an intrauterine growth restriction (IUGR) neonate, eight (57.2%) were TNFRSF6-670*G homozygous as opposed to 3 (17.6%) of 17 pre-eclamptics who did not have IUGR (P = 0.03) and 19 (21.3%) normotensive controls (P = 0.008). Carriage of the TNFRSF6-670 polymorphism in the neonate was not associated with pre-eclampsia or IUGR. Maternal possession of the TNFRSF6-670*G increases the risk for pre-eclampsia and pre-eclampsia-associated IUGR in women who deliver at < 37 weeks.

The purpose of this study was to determine serum a 2 -HS glycoprotein (AHSG) concentration and its diagnostic accuracy in preeclampsia. In this case-control study, the serum C-reactive protein (CRP) and AHSG levels were measured in 93 preeclamptic patients and in 127 healthy pregnant women by immunoturbidimetry and radial immunodiffusion. The serum CRP levels were significantly higher, whereas the serum AHSG concentrations were significantly lower in the preeclamptic group than in the control group (median (25th to 75th percentile), CRP: 6.71 mg l À1 (2.76-12.69) vs. 3.38 mg l À1 (1.69-7.27), respectively; AHSG: 660 lg ml À1 (612-768) vs. 744 lg ml À1 (660-816), respectively; Po0.001 for both). In preeclamptic patients, the serum AHSG concentrations showed significant inverse correlations with systolic blood pressure and serum CRP levels. A low serum AHSG level (p720 lg ml À1 ) was significantly associated with preeclampsia (adjusted odds ratio (95% confidence interval): 3.69 (1.82-7.51); Po0.001). According to the receiver operating characteristic curves, the measurement of serum AHSG concentrations was as accurate as that of serum CRP levels to detect preeclampsia. In conclusion, serum AHSG concentration is decreased and reflects-at least partly-systemic inflammation in preeclampsia.