The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth

J Reprod Immunol. 2010 Dec;87(1-2):67-73. doi: 10.1016/j.jri.2010.05.006.

Abstract

Anti-paternal HLA-antibodies are considered a harmless phenomenon during most pregnancies, whereas their role in recurrent miscarriage (RM) patients is disputed. In contrast to primary RM, patients with secondary RM have carried a fetus to term pregnancy prior to a series of miscarriages, which increases the chance that allogeneic fetal cells appear in the maternal circulation. This study investigates the frequency of HLA-antibodies in secondary RM, primary RM patients and parous controls and analyzes whether the presence of HLA-antibodies in early pregnancy is associated with pregnancy outcome. Sera from women with secondary RM (n=56), primary RM (n=13) and parous controls (n=24) were tested for HLA-antibodies using an ELISA assay and complement dependent cytotoxicity. Samples were taken at gestational week 4-5 in 62 (90%) of the patients. HLA-antibodies were significantly more frequent in secondary RM patients with a boy prior to the miscarriages (62%) compared to secondary RM patients with a firstborn girl (29%, p=0.03), primary RM patients (23%, p=0.02) and parous controls (25%, p=0.005). Forty-one percent of HLA-antibody positive pregnant RM patients had a live birth compared to 76% of HLA-antibody negative RM patients, p=0.006 (adjusted OR: 0.22 (0.07-0.68), p=0.008). In conclusion, HLA-antibodies are significantly more frequent in secondary RM patients with a firstborn boy than in other RM patients and controls. The presence of these antibodies in early pregnancy is associated with a reduced chance of a live birth. Further exploring this association may increase our understanding of maternal acceptance of the fetal allograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Habitual / genetics
  • Abortion, Habitual / immunology*
  • Adult
  • Antibody Specificity
  • Cytotoxicity Tests, Immunologic
  • Enzyme-Linked Immunospot Assay
  • Female
  • HLA Antigens / immunology*
  • Histocompatibility Testing
  • Histocompatibility, Maternal-Fetal*
  • Humans
  • Immune Tolerance
  • Isoantibodies / blood*
  • Isoantibodies / immunology
  • Live Birth
  • Odds Ratio
  • Pregnancy / immunology*
  • Pregnancy Outcome
  • Sex Characteristics
  • Young Adult

Substances

  • HLA Antigens
  • Isoantibodies