17β-Estradiol Promotes Proinflammatory and Procoagulatory Phenotype of Innate Immune Cells in the Presence of Antiphospholipid Antibodies.

Gayane Manukyan,Gayane Manukyan,Gayane Manukyan,Gayane Manukyan,Gayane Manukyan,Eva Kriegova,Eva Kriegova,Ludek Slavik,Anush Martirosyan,Anush Martirosyan,Anush Martirosyan,Martin Dihel,Martin Dihel,Tomas Papajik,Jana Ulehlova,Jana Ulehlova

doi:10.3390/biomedicines8060162

Abstract

Antiphospholipid syndrome (APS) is the most common cause of acquired thrombophilia and recurrent spontaneous miscarriages associated with extended persistence of antiphospholipid antibodies (aPL). How circulating aPL and high-17β-estradiol (E2) environment contribute to the pregnancy complications in APS is poorly defined. Therefore, we aimed to analyse whether E2 could be responsible for the immune cell hyperactivation in aPL- positive (lupus anticoagulant, anti-cardiolipin, anti-β2-glycoprotein) in women. For this, peripheral blood mononuclear cells (PBMCs) from 14 aPL- positive and 13 aPL- negative women were cultured in the presence or absence of E2, LPS or E2+LPS and cell immunophenotype and cytokine release were analysed. In the aPL+ group, E2 presence markedly increased the percentage of NK cells positive for CD69 (p < 0.05), monocytes positive for tissue factor (TF, CD142) (p < 0.05), and B cells expressing PD-L1 (p < 0.05), as well as the elevated production of IL-1β comparing to aPL- women (p < 0.01). Regardless of aPL positivity, E2 augmented the procoagulatory response elicited by LPS in monocytes. Our findings show the ability of E2 to promote proinflammatory and procoagulatory phenotype of innate immune cells in individuals with aPL positivity. Our data highlights the significant impact of female hormones on the activation of immune cells in the presence of aPL.

Highlights

Antiphospholipid syndrome (APS) is an acquired autoimmune condition mediated by a heterogeneous group of autoantibodies [1,2]
Our results showed that E2 alone induced tissue factor (TF, CD142, or thromboplastin) response by monocytes only from aPL+ donors (p < 0.05) (Figure 1)
TF is the primary trigger of coagulation which is inducible by aPL, thereby promoting thrombosis [5,24]

Summary

Introduction

Antiphospholipid syndrome (APS) is an acquired autoimmune condition mediated by a heterogeneous group of autoantibodies [1,2]. The presence of antiphospholipid antibodies (aPL), anti-β2 glycoprotein I (anti-β2GPI), anti-cardiolipin (aCL), and lupus anticoagulant (LA), is a serological marker of APS. The syndrome covers a spectrum of clinical manifestations ranging from vascular thrombotic events to recurrent pregnancy losses and other obstetric complications [3]. Numerous epidemiological and clinical evidence has suggested a positive association between aPL and thrombotic complications in APS patients [1,2]. The syndrome can be diagnosed as “primary” when there is no evidence of any underlying autoimmune processes, or “secondary” if accompanied by other autoimmune diseases, with systemic lupus erythematosus (SLE) being the most common coexisting condition [6]. APS commonly affects women in childbearing age [7], causing significant maternal morbidity and mortality in pregnant women, including recurrent miscarriages, stillbirth or premature birth, preeclampsia, eclampsia, and placental insufficiency [8]

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