Antiphospholipid antibodies affect trophoblast gonadotropin secretion and invasiveness by binding directly and through adhered beta(2)-glycoprotein I

Objective, To investigate the in vitro ability of antiphospholipid antibodi es (aPL) to bind human trophoblast cells and to affect gonadotropin secreti on and invasiveness. Methods, Antiphospholipid antibody IgG from women with recurrent miscarriag es, beta(2)-glycoprotein I (beta(2)GPI)-independent IgG aPL human monoclona l antibody (mAb) (519), and IgM anti-beta(2)GPI human mAb (TM1G2) were inve stigated for their binding to trophoblasts cultured for various amounts of time, their ability to affect invasiveness of Matrigel-coated filters, and their release of human chorionic gonadotropin (hCG), Results, Polyclonal IgG aPL, as well as mAb 519 and TM1G2, bound to trophob lasts, the highest binding being found when cells displayed the greatest am ount of syncytium formation. TM1G2 binding was found to be beta(2)GPI depen dent. Both polyclonal and monoclonal aPL, but not the controls, significant ly reduced hCG release and Matrigel invasiveness. Conclusion. These findings suggest that aPL recognition of both anionic PL and adhered beta(2)GPI on trophoblast cell structures might represent a pot ential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome.