A possible coagulation-independent mechanism for pregnancy loss involving β(2) glycoprotein 1-dependent antiphospholipid antibodies and CD1d

Am J Reprod Immunol. 2012 Jan;67(1):54-65. doi: 10.1111/j.1600-0897.2011.01028.x. Epub 2011 Jun 20.

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.

MeSH terms

  • Abortion, Habitual / etiology
  • Abortion, Habitual / immunology*
  • Abortion, Habitual / pathology
  • Antibodies, Antiphospholipid / adverse effects
  • Antibodies, Antiphospholipid / immunology*
  • Antibodies, Antiphospholipid / metabolism
  • Antigens, CD1d / genetics
  • Antigens, CD1d / immunology*
  • Antiphospholipid Syndrome / complications
  • Antiphospholipid Syndrome / immunology*
  • Antiphospholipid Syndrome / pathology
  • Cell Line, Tumor
  • Choriocarcinoma / immunology
  • Choriocarcinoma / pathology
  • Coculture Techniques
  • Cross-Linking Reagents
  • Decidua / cytology
  • Decidua / drug effects
  • Decidua / immunology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoprecipitation
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / immunology
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*
  • Phosphatidylserines / immunology
  • Phosphatidylserines / metabolism
  • Pregnancy
  • Trophoblasts / cytology
  • Trophoblasts / drug effects
  • Trophoblasts / immunology*
  • beta 2-Glycoprotein I / immunology*

Substances

  • Antibodies, Antiphospholipid
  • Antigens, CD1d
  • CD1D protein, human
  • Cross-Linking Reagents
  • Phosphatidylserines
  • beta 2-Glycoprotein I
  • Interleukin-12
  • Interferon-gamma