1. A Possible Coagulation-Independent Mechanism for Pregnancy Loss Involving β2glycoprotein 1-Dependent Antiphospholipid Antibodies and CD1d
- Author
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Danny J. Schust, Shiho Miura, Tomoyuki Fujii, Yuji Taketani, Kei Kawana, Takahiro Yamashita, Hironobu Hyodo, Takeshi Nagamatsu, Yuki Iwasawa, Shiro Kozuma, Seisuke Sayama, Junko Matsumoto, Yukiko Kawana, and Katsuyuki Adachi
- Subjects
medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,chemical and pharmacologic phenomena ,Inflammation ,Monoclonal antibody ,Antiphospholipid syndrome ,Internal medicine ,medicine ,Immunology and Allergy ,biology ,Obstetrics and Gynecology ,Trophoblast ,hemic and immune systems ,medicine.disease ,Molecular biology ,medicine.anatomical_structure ,Cytokine ,Endocrinology ,Reproductive Medicine ,CD1D ,Interleukin 12 ,biology.protein ,Antibody ,medicine.symptom - Abstract
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 β2glycoprotein 1-dependent antiphospholipid antibodies and CD1d. Am J Reprod Immunol 2012; 67: 54–65 Problem 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.
- Published
- 2011
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