title: Cell-free nucleic acids in (maternal) blood: any relevance to (reproductive) immunologists?
abstract: Cell-free foetal DNA recently hit the international headlines by facilitating the non-invasive prenatal testing (NIPT) of foetal chromosomal anomalies directly from maternal blood samples. Being largely of placental origin, cell-free foetal DNA may also, however, provide insight into underlying pathological changes in preeclampsia, or the influences of external stresses, such as hypoxia. This analysis may be enhanced by the simultaneous assessment of placenta-derived, cell-free mRNA species. The source of maternal cell-free DNA is not readily apparent, but may involve neutrophil extracellular traps (NETs). The rapid rise in this material following removal of the placenta, especially in preeclampsia, may indicate a rapid transient maternal inflammatory response to placenta-derived debris. Since NETs have recently been shown to promote coagulation, this may provide a link to pregnancy-associated thrombosis or placental infarction. The presence of cell-free, placenta-derived DNA may not be as innocuous as commonly assumed, as it is largely hypomethylated and could, like bacterial DNA, trigger the activation of maternal immune effector cells via interaction with toll-like receptor 9 (TLR9), thereby contributing to an excessive inflammatory response in preeclampsia or preterm labour. Possibly the most fascinating aspect concerning placenta-derived, cell-free nucleic acids is the recent report that placental exosomes loaded with placenta-specific C19MC miRNA species may modulate the antiviral response of maternal immune cells, thereby ensuring foetal well-being.
authors.affiliation: Laboratory for Prenatal Medicine, Department of Biomedicine, University Hospital Basel, CH-4031 Basel, Switzerland. Electronic address: sinuhe.hahn@usb.ch.
authors.forename: Sinuhe
authors.initials: S
authors.lastname: Hahn
authors.affiliation: Laboratory for Prenatal Medicine, Department of Biomedicine, University Hospital Basel, CH-4031 Basel, Switzerland; Department of Rheumatology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Stavros
authors.initials: S
authors.lastname: Giaglis
authors.affiliation: Division of Hematology, Department of Internal Medicine, University Hospital Basel; Blood Transfusion Centre, Swiss Red Cross, Basel, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Buser
authors.affiliation: Department Obstetrics, University Women's Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: Irene
authors.initials: I
authors.lastname: Hoesli
authors.affiliation: Department Obstetrics, University Women's Hospital Basel, CH-4031 Basel, Switzerland.
authors.forename: Olav
authors.initials: O
authors.lastname: Lapaire
authors.affiliation: Department of Rheumatology, Kantonsspital Aarau, Aarau, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Hasler
mesh_terms: D000818:Animals; D004247:DNA / Q000097:blood / Q000276:immunology; D055354:Exosomes / Q000276:immunology / Q000378:metabolism; D065206:Extracellular Traps / Q000276:immunology / Q000378:metabolism; D005260:Female; D006801:Humans; D010920:Placenta / Q000276:immunology / Q000378:metabolism; D011225:Pre-Eclampsia / Q000097:blood / Q000276:immunology; D011247:Pregnancy; D047928:Premature Birth / Q000097:blood / Q000276:immunology; D012333:RNA, Messenger / Q000097:blood / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000276:immunology / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA
keywords: Cell-free DNA; Neutrophil extracellular traps (NETs); Placenta; miRNA