Problem-Women with antiphospholipid antibodies (aPL) are at risk for recurrent miscarriage, preeclampsia and preterm labor. aPL target the placenta directly by binding to Beta 2 -Glycoprotein I (β 2 GPI) expressed on the surface of trophoblast cells. The objective of this study was to determine the effects of aPL on trophoblast function and the mechanisms involved.Method of study-First trimester trophoblast were treated with anti-β 2 GPI monoclonal antibodies and patient-derived aPL, after which cell survival and function was evaluated.Results-We report that anti-β 2 GPI antibodies trigger an inflammatory response in trophoblast, characterized by increased secretion of IL-8, MCP-1, GRO-α and IL-1β, and that this occurs in a TLR-4/MyD88-dependent manner. At high concentrations, these antibodies also induce caspasemediated cell death. This was attenuated upon disabling of the MyD88 pathway, suggesting that anti-β 2 GPI-induced inflammatory mediators compromise trophoblast survival by acting in an autocrine/ paracrine manner. Enhanced IL-8, GRO-α and IL-1β secretion also occured when trophoblast were incubated with antibodies from patients with antiphospholipid syndrome. Heparin, which acts as a pro-survival factor in human trophoblast, attenuated the anti-β 2 GPI antibody-mediated cell death, and also the pro-inflammatory response, but only at high concentrations.Conclusions-These findings demonstrate that aPL triggers a placental inflammatory response via the TLR-4/MyD88 pathway, which in turn compromises trophoblast survival. Thus, the TLR-4/ MyD88 pathway may provide a new therapeutic target to improve pregnancy outcome in antiphospholipid syndrome patients.
Understanding the specific barriers to vaccination that our population faced was helpful in designing the interventions to improve knowledge and acceptance of influenza vaccination in pregnancy, which led to an increased vaccination rates in women.
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