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Abstract: Cell‐free self‐DNA or RNA may induce an immune response by activating specific sensing receptors. During pregnancy, placental nucleic acids present in the maternal circulation further activate these receptors due to the presence of unmethylated CpG islands. A higher concentration of cell‐free foetal DNA is associated with pregnancy complications and a higher risk for foetal rejection. Cell‐free foetal DNA originates from placental trophoblasts. It appears in different forms: free, bound to histones in nucleosomes, in neutrophil extracellular traps (NETs) and in extracellular vesicles (EVs). In several pregnancy complications, cell‐free foetal DNA triggers the production of proinflammatory cytokines, and this production results in a cellular and humoral immune response. This review discusses preeclampsia, systemic lupus erythematosus, foetal growth restriction, gestational diabetes, rheumatoid arthritis and obesity in pregnancy from an immunological point of view and closely examines the different pathways that result in maternal inflammation. Understanding the role of cell‐free nucleic acids, as well as the biogenesis of NETs and EVs, will help us to specify their functions or targets, which seem to be important in pregnancy complications. It is still not clear whether higher concentrations of cell‐free nucleic acids in the maternal circulation are the cause or consequence of various complications. Therefore, further clinical studies and, even more importantly, animal experiments that focus on the involved immunological pathways are needed. [ABSTRACT FROM AUTHOR]

Cell-free fetal DNA in maternal circulation is higher during preeclampsia. It is unclear whether it is the cause or the consequence of the disease. The aim of this study was to prove whether injected rat fetal DNA induces preeclampsia-like symptoms in pregnant Wistar rats. They received daily i.p. injections of water or rat fetal DNA (400 μg) from gestation day 14 to 18. Blood pressure, proteinuria, placental and fetal weight were measured at gestation day 19. Plasma DNase activity, proteinuria and creatinine clearance were assessed. There was no significant difference in any of the measured parameters. The results of this study do not confirm the hypothesis that fetal DNA might induce preeclampsia. This is in contrast to others using human fetal DNA in mice. Further studies should be focused on the effects of fetal DNA from the same species protected from DNase activity. [ABSTRACT FROM PUBLISHER]

Abstract: Background: The receptor for advanced glycation end-products (RAGEs) and its gene polymorphisms are implicated in the pathogenesis of different chronic diseases including diabetes and its complications. Infant formulas contain high amounts of advanced glycation end-products (AGEs) — the ligands of RAGE. Methods: In this cross-sectional study, we examined the impact of G82S and −374 A/T polymorphisms in the gene encoding RAGE on standard blood chemistry, soluble (s)RAGE and inflammatory markers in 244 healthy infants (3–16months of age) and in 119 healthy mothers. Children were subdivided according to age (younger and older than 8months) and for the −374 A/T polymorphism according to the feeding regimen (breast-fed vs. infant formula-fed). Results: Minor allele of the RAGE gene polymorphism G82S was associated with reduced plasma sRAGE in all age groups and with increased sICAM-1 in older children and mothers. Minor allele carrying mothers had decreased insulin sensitivity and HDL. The A allele of the RAGE gene promoter polymorphism −374 A/T was associated with higher indices of insulin resistance in young infant formula-fed, but not breast-fed children. In older, formerly infant formula-fed children signs of insulin resistance diminished, while formerly breast-fed children with A allele were more insulin sensitive. Conclusions: The phenotype of minor allele carriers in G82S is associated with reduced levels of protective sRAGE in healthy infants. With increasing age sICAM-1 levels increased and insulin resistance developed. In early childhood the phenotype of the −374 A/T polymorphism was diet-dependently associated with changes in glucose metabolism, which diminished with increasing age. [Copyright &y& Elsevier]