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

• Published in: Biomedicines 2020-06, Vol.8 (6), p.162
• Main Authors: Manukyan, Gayane, Martirosyan, Anush, Slavik, Ludek, Ulehlova, Jana, Dihel, Martin, Papajik, Tomas, Kriegova, Eva
• Format: Article
• Language: English
• Subjects: 17β-Estradiol; Antibodies; Anticoagulants; Antiphospholipid antibodies; Antiphospholipid syndrome; Arthritis; Autoimmune diseases; Cardiolipin; CD69 antigen; Cell activation; Cloning; Cytokines; estradiol; Flow cytometry; IL-1β; in vitro; Inflammation; Leukocytes (mononuclear); Lipopolysaccharides; Lupus; Lymphocytes; Lymphocytes B; Monocytes; PD-L1 protein; Peripheral blood mononuclear cells; Phenotypes; Pregnancy; Pregnancy complications; Software; Thrombophilia; Tissue factor; Tumor necrosis factor-TNF; Womens health
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines8060162

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.