Vital Mechanism of NETs Formation vs. Suicidal Mechanism of NETs Formation During Normal Pregnancy and Preeclampsia

A Retrospective Study of Vital Mechanism of NETs Formation vs. Suicidal Mechanism of NETs Formation During Normal Pregnancy and Preeclampsia

Formation of neutrophil extracellular traps (NETs) is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Two mechanisms of formation of NETs are described in the literature: vital mechanism via Toll Like Receptors (TLRs) and suicidal mechanism, dependent on the reactive oxygen species (ROS) pathway. The description of these two mechanisms of formation of NETs is recent and no data exist in the context of pregnancy.

This is a descriptive pilot study on a ready-constituted biobank. It is an ancillary study to a previous cohort (RCB number: 2014-A01120-47, NCT01736826).

Pregnancy generates an increased risk of thrombosis, and placenta-mediated diseases constitute a risk factor for cardiovascular pathologies responsible for significant maternal-fetal morbidity and mortality. Understanding and exploring the cellular and molecular mechanisms of dysfunctions of the vascular-placental interface could provide arguments to understand the systemic vascular risk, characterize it and finally detect it on the basis of new markers, thus opening the way for targeted preventive management to reinforce the general principles of precision medicine.

Formation of NETs is a process of activation of neutrophils, which then generate filaments containing DNA, enzymes and extracellular histones. Formation of NETs occurs in pregnancy and is increased in vascular-placental complications. It can be studied by measuring circulating histones, particularly the citrullinated histone H3. Levels of this modified histone H3, as well as those of two other modifications, have recently been shown to increase during pregnancy. These levels have also been shown to be even greater in pregnancy complications.

Furthermore, two mechanisms of formation of NETs are described in the literature: vital mechanism via Toll Like Receptors (TLRs) and suicidal mechanism, dependent on the reactive oxygen species (ROS) pathway. The description of these two mechanisms of formation of NETs is recent and no data exist in the context of pregnancy.

The aim of this study is to describe the part of these two mechanisms in normal and complicated pre-eclampsia pregnancies in order to obtain a better physiopathological knowledge of pre-eclampsia to propose new circulating biomarkers and to develop new therapeutic strategies for placental vascular pathologies.

Not applicable as this study is on samples from a biobank.

Inclusion criteria:

The inclusion criteria for the previous cohort (NCT01736826) were:

• pregnant women followed at Nimes University hospital for normal pregnancy or pregnancy with placental vascular pathology (pre-eclampsia and/or intra-uterine growth retardation).
• The patient must have given her free and informed consent and signed the consent form.
• The patient must be a member or beneficiary of a health insurance plan
• Only women are included
• Patients are at least 18 years old

Exclusion Criteria:

Not applicable as this is a study on samples from a biobank. The non-inclusion criteria of the previous cohort (NCT01736826) were :

• twin pregnancies.