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Master Thesis

Marqueurs de NETs dans les pathologies vasculaires placentaires

Abstract : Placental vascular pathologies refer to vascular complications associated with a dysregulated maternal-blood circulation causes by an abnormal placental vascularization. These pathologies frequently involve thrombophilia. For example, patients with antiphospholipid syndrome, a hypercoagulable state, are severely affected by these pregnancy-related complications. Thrombophilia is also a risk factor for recurrent early pregnancy loss, another common obstetric disorder. However, thrombophilia does not explain all placental vascular pathologies and recurrent early pregnancy losses. Some patients are indeed free of the biological markers of thrombophilia (presence of antiphospholipids; deficiency in antithrombin, protein C or protein S; activated protein C resistance; factor V Leiden or factor II mutations; or hyperhomocysteinemia), suggesting that these conditions may be driven by another underlying mechanism. Neutrophil Extracellular Traps (NETs) are networks of decondensed chromatin and proteins released by polymorphonuclear neutrophils actively involved in thrombosis, including the antiphospholipid syndrome. No study has yet investigated the relationship between NETs and PVP/REPL. According to recent observations on the pathogenic potential of the compounds on endothelial and trophoblastic cells, we hypothesized that NETs are involved in the onset of PVP/REPL in patients without thrombophilia. More precisely, that patients with PVP/REPL free of thrombophilia have increased baseline levels of NETs compared to healthy controls and have similar levels to those achieved in patients with obstetric APS. The aim of this study was thus to compare plasma levels of several NET biomarkers (cell-free DNA, MPO-DNA complexes, citrullinated histones H3, and DNase) of patients with a history of unexplained PVP or REPL with (1) healthy controls, and (2) patients with obstetric APS or unconfirmed antiphospholipid antibodies. We found significantly higher levels of MPO-DNA complexes and DNase in patients with unexplained PVP/REPL compared to healthy controls. Conversely, levels of citrullinated histones H3 and cell-free DNA were significantly higher in healthy controls than in the study patients. There was no difference in NETs levels according to the antiphospholipid antibody status (no antiphospholipid antibodies, intermittent or unconfirmed antiphospholipid antibodies at 12 weeks, or confirmed obstetric antiphospholipid syndrome). As previous studies have shown that NET biomarkers such as MPO-DNA complexes were increased in antiphospholipid syndrome, these results appear to be consistent with our hypothesis of increased baseline NETs levels in patients without thrombophilia. The lower levels of NETs found in patients compared to healthy controls may reflect the lack of sensitivity of some NETs biomarkers to evaluate NETosis. Further studies with larger sample sizes, prospective follow-ups and a control group of women with a history of non-complicated pregnancies are required to confirm these results.
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Submitted on : Monday, December 14, 2020 - 3:46:45 PM
Last modification on : Tuesday, January 26, 2021 - 3:10:16 AM
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  • HAL Id : dumas-03064858, version 1




Thomas Vidal. Marqueurs de NETs dans les pathologies vasculaires placentaires. Sciences du Vivant [q-bio]. 2020. ⟨dumas-03064858⟩



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