Objective. To investigate the in vitro ability of antiphospholipid antibodies (aPL) to bind human trophoblast cells and to affect gonadotropin secretion and invasiveness.Methods. Antiphospholipid antibody IgG from women with recurrent miscarriages, ␤ 2 -glycoprotein I (␤ 2 GPI)-independent IgG aPL human monoclonal antibody (mAb) (519), and IgM anti-␤ 2 GPI human mAb (TM1G2) were investigated 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 trophoblasts, the highest binding being found when cells displayed the greatest amount of syncytium formation. TM1G2 binding was found to be ␤ 2 GPI dependent. Both polyclonal and monoclonal aPL, but not the controls, significantly reduced hCG release and Matrigel invasiveness.Conclusion. These findings suggest that aPL recognition of both anionic PL and adhered ␤ 2 GPI on trophoblast cell structures might represent a potential pathogenetic mechanism for defective placentation in women with the antiphospholipid syndrome.

Vaginal ecosystem study with the detection of pathogens is a key instrument in the prevention of preterm delivery, pPROM, chorioamnionitis, neonatal, puerperal and maternal-fetal infections.

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Background: Antiphospholipid antibodies reacting with b2-glycoprotein I (b2GPI) have been associated with recurrent fetal loss and pregnancy complications. Objective: To investigate whether specific mutations in the phospholipid binding site of b2GPI might affect its binding to trophoblast and in turn the anti-b2GPI antibody induced functional effects. Methods: b2GPI adhesion to trophoblast was evaluated as human monoclonal IgM or polyclonal IgG antib2GPI antibody binding to trophoblast monolayers cultured (1) in complete medium; (2) in serum-free medium; (3) after serum starvation in the presence of purified human b2GPI; or (4) in the presence of b2GPI with single or multiple mutations in the amino acid loop Cys 281 -Lys-Asn-Lys-Glu-Lys-Lys-Cys 288 . The effect of anti-b2GPI binding to trophoblast was evaluated as chorionic gonadotropin (hCG) mRNA expression, and protein release by RT-PCR and radioimmunoassay, respectively. Results: b2GPI adhesion to trophoblast and its consequent recognition by the specific antibodies were inversely proportional to the mutation number in the phospholipid binding site. Anti-b2GPI antibodies reduced gonadotropin release, hormone dependent hCG mRNA expression, and protein synthesis in the presence of b2GPI, while the addition of the mutants or the absence of b2GPI had no effect. Conclusions: b2GPI binds to trophoblast in vitro through its fifth domain, as reported for endothelial cells, and can be recognised by anti-b2GPI antibodies; the antibody binding downregulates trophoblast hCG synthesis and secretion. Such a mechanism might contribute to defective placentation in women with fetal loss associated with the antiphospholipid syndrome.