Iwasawa Y, Kawana K, Fujii T, Schust DJ, Nagamatsu T, Kawana Y, Sayama S, Miura S, Matsumoto J, Adachi K, Hyodo H, Yamashita T, Kozuma S, Taketani Y. A possible coagulation-independent mechanism for pregnancy loss involving β2glycoprotein 1-dependent antiphospholipid antibodies and CD1d. Am J Reprod Immunol 2012; 67: 54–65Problem
β2glycoprotein1 (β2GP1)-dependent antiphospholipid antibodies (aPL) increase the risk for recurrent pregnancy loss. We address whether anti-β2GP1 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 β2GP1. Anti-β2GP1 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-β2GP1 mAb to co-cultures resulted in a three-fold increase in IL12p70 secretion. IFNγ secretion from decidual lymphocytes was also induced during co-culture with anti-β2GP1 mAbs.Conclusions
β2GP1-dependent IL12 release from CD1d-bearing trophoblast in the presence of aPL may link the antiphospholipid syndrome to pregnancy loss via an inflammatory mechanism.