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A Possible Coagulation‐Independent Mechanism for Pregnancy Loss Involving β 2 glycoprotein 1‐Dependent Antiphospholipid Antibodies and CD1d
Author(s) -
Iwasawa Yuki,
Kawana Kei,
Fujii Tomoyuki,
Schust Danny J.,
Nagamatsu Takeshi,
Kawana Yukiko,
Sayama Seisuke,
Miura Shiho,
Matsumoto Junko,
Adachi Katsuyuki,
Hyodo Hironobu,
Yamashita Takahiro,
Kozuma Shiro,
Taketani Yuji
Publication year - 2012
Publication title -
american journal of reproductive immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.071
H-Index - 97
eISSN - 1600-0897
pISSN - 1046-7408
DOI - 10.1111/j.1600-0897.2011.01028.x
Subject(s) - trophoblast , cd1d , immunology , antibody , biology , cytokine , antiphospholipid syndrome , microbiology and biotechnology , natural killer t cell , immune system , t cell , placenta , pregnancy , fetus , genetics
Citation 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 β 2 glycoprotein 1‐dependent antiphospholipid antibodies and CD1d. Am J Reprod Immunol 2012; 67: 54–65 Problem β 2 glycoprotein1 (β 2 GP1)‐dependent antiphospholipid antibodies (aPL) increase the risk for recurrent pregnancy loss. We address whether anti‐β 2 GP1 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 β 2 GP1. Anti‐β 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‐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 β 2 GP1‐dependent IL12 release from CD1d‐bearing trophoblast in the presence of aPL may link the antiphospholipid syndrome to pregnancy loss via an inflammatory mechanism.