title: A possible coagulation-independent mechanism for pregnancy loss involving β(2) glycoprotein 1-dependent antiphospholipid antibodies and CD1d.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Iwasawa
authors.forename: Kei
authors.initials: K
authors.lastname: Kawana
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujii
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Schust
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nagamatsu
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kawana
authors.forename: Seisuke
authors.initials: S
authors.lastname: Sayama
authors.forename: Shiho
authors.initials: S
authors.lastname: Miura
authors.forename: Junko
authors.initials: J
authors.lastname: Matsumoto
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Adachi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Hyodo
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamashita
authors.forename: Shiro
authors.initials: S
authors.lastname: Kozuma
authors.forename: Yuji
authors.initials: Y
authors.lastname: Taketani
mesh_terms: D000026:Abortion, Habitual / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D017152:Antibodies, Antiphospholipid / Q000009:adverse effects / Q000276:immunology* / Q000378:metabolism; D055610:Antigens, CD1d / Q000235:genetics / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000150:complications / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D002822:Choriocarcinoma / Q000276:immunology / Q000473:pathology; D018920:Coculture Techniques; D003432:Cross-Linking Reagents; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D010718:Phosphatidylserines / Q000276:immunology / Q000378:metabolism; D011247:Pregnancy; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D053482:beta 2-Glycoprotein I / Q000276:immunology*
chemical_list: D017152:Antibodies, Antiphospholipid; D055610:Antigens, CD1d; C526877:CD1D protein, human; D003432:Cross-Linking Reagents; D010718:Phosphatidylserines; D053482:beta 2-Glycoprotein I; D018664:Interleukin-12; D007371:Interferon-gamma