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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT05470712

Acronym

GrossNETs

Enrollment

Registered

2022-07-22

Start date

2022-07-20

Completion date

2022-12-31

Last updated

2025-12-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pre-Eclampsia

Keywords

Pregnancy, Pre-eclampsia, Neutrophils, Extracellular traps

Brief summary

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.

Detailed description

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.

Interventions

None listed

Study design

Observational model

CASE_CONTROL

Time perspective

RETROSPECTIVE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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.

Design outcomes

Primary

Measure	Time frame	Description
To evaluate vital mechanism of NETs formation between pregnant women with normal pregnancies and those developing preeclampsia.	3 months	Evaluation of vital mechanism of NETs formation between pregnant women with normal pregnancies and those developing preeclampsia.

Secondary

Measure	Time frame	Description
To compare the proportion of vital mechanism of NETs formation in the presence of a TLR-blocking antibody between pregnant women with normal pregnancies and those developing preeclampsia.	3 months	Evaluation of the proportion of vital mechanism of NETs formation in the presence of a TLR-blocking antibody between pregnant women with normal pregnancies and those developing preeclampsia.
To compare vital and suicidal mechanisms of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.	3 months	Evaluation of vital and suicidal mechanisms of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
To compare vital and suicidal mechanisms of NETs formation in the presence or absence of a TLR blocking antibody or ROS inhibitor (DPI) separately within each group: normal pregnancy and preeclamptic pregnancy.	3 months	Evaluation of vital and suicidal mechanisms of NETs formation in the presence or absence of a TLR blocking antibody or ROS inhibitor (DPI) separately within each group: normal pregnancy and preeclamptic pregnancy.
To compare the proportion of vital mechanism of NETs formation in the presence or absence of a TLR-blocking antibody within each group: normal pregnancy and preeclamptic pregnancy.	3 months	Evaluation of the proportion of vital mechanism of NETs formation in the presence or absence of a TLR-blocking antibody within each group: normal pregnancy and preeclamptic pregnancy.
To compare the proportion of suicidal mechanism of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.	3 months	Evaluation of the proportion of suicidal mechanism of NETs formation between pregnant women with a normal pregnancy and those developing preeclampsia.
To compare suicidal mechanism of NETs formation in the presence or absence of ROS inhibitor (PGD) separately within each group: normal pregnancy and preeclamptic pregnancy.	3 months	Evaluation of suicidal mechanism of NETs formation in the presence or absence of ROS inhibitor (PGD) separately within each group: normal pregnancy and preeclamptic pregnancy.
To compare the proportion of suicidal mechanism of NETs formation in the presence of an ROS inhibitor (PGD) between pregnant women with a normal pregnancy and those developing preeclampsia.	3 months	Evaluation of the proportion of suicidal mechanism of NETs formation in the presence of an ROS inhibitor (PGD) between pregnant women with a normal pregnancy and those developing preeclampsia
To compare vital and suicidal mechanisms of NETs formation in the presence of TLR blocking antibody or ROS inhibitor (DPI) between pregnant women with normal pregnancy and those developing preeclampsia.	3 months	Evaluation of vital and suicidal mechanisms of NETs formation in the presence of TLR blocking antibody or ROS inhibitor (DPI) between pregnant women with normal pregnancy and those developing preeclampsia.

Countries

France

Outcome results