A Possible Coagulation-Independent Mechanism for Pregnancy Loss Involving ß2glycoprotein 1-Dependent Antiphospholipid Antibodies and CD1d

Problem beta(2)glycoprotein1 (beta(2)GP1)-dependent antiphospholipid antibodies (aPL) increase the risk for recurrent pregnancy loss. We address whether antib2GP1 antibodies can interact with phosphatidylserine (PS)-bearing CD1d on trophoblast cells and induce local inflammation. Methods CD1d-bearing choriocarcinoma cells were used in flow cytometry and immunoprecipitation experiments. CD1d-mediated cytokine induction was assessed using antibody cross-linking. Cytokine production during co-culture of decidual lymphocytes with CD1d-bearing cells was also examined. Results Trophoblast surface-expressed CD1d forms a complex with PS-bound beta(2)GP1. Anti-beta(2)GP1 mAb cross-linking causes IL12p70 release from CD1d-bearing cells. IL12p70 release from CD1d-bearing trophoblast cells was also induced during co-culture with human decidual lymphocytes. The addition of anti-b2GP1 mAb to co-cultures resulted in a three-fold increase in IL12p70 secretion. IFN gamma secretion from decidual lymphocytes was also induced during co-culture with anti-b2GP1 mAbs. Conclusions b2GP1-dependent IL12 release from CD1d-bearing trophoblast in the presence of aPL may link the antiphospholipid syndrome to pregnancy loss via an inflammatory mechanism.