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

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.

Correlation of Insulin Like Growth Factor-1 and Insulin-Like Growth Factor Binding Protein with LH, FSH and Testosterone in Iraqi Children with Growth Hormone Deficiency

“…It is hypothesized that endogenous IGF-I may function as a stimulatory metabolic signal to the pubertal ovine hypothalamo-pituitary axis because exogenous IGF-I has been found to stimulate luteinizing hormone (LH) secretion. In adults, FSH and testosterone promote IGFBP-3 proteolysis to improve IGF-1 activity for maturation of germ cells, which may not be the case in the age group included in this study [14].…”

“…They play a role in desire and sexual excitement, and they also prevent early uterine contraction in pregnant women by relaxing the myometrium's muscles. And in both men and women, they serve as the building blocks for estrogens [14].…”

Impact of HLA Class I Antigen, Killer Inhibitory Receptor, and FCGR3A Genotypes on Breast Cancer Susceptibility and Tumor Stage

“…Interindividual variability in the NK receptors repertoire is also influenced by KIR genes, HLA class I alleles, and FCGR3A (CD16A) genetic polymorphisms. The presence of steroid hormone receptors, including ER (estradiol E2), mediates immunostimulation or immunosuppression, particularly on NK cells in a timedependent manner [30][31][32].…”

Influence of Antiphospholipid Antibody-Associated Thrombophilia on the Risk of Preterm Birth: A Systematic Review

“…At the background of this condition lies the persistent presence of antiphospholipid antibodies (aPL)–lupus anticoagulant, anticardiolipin antibodies, and anti-β2-glycoprotein I antibodies [ 8 ]. These antibodies promote a pro-thrombotic state by interfering with the coagulation cascade and endothelial function, thereby increasing the risk of vascular complications [ 9 ].…”