Association of HY-restricting HLA class II alleles with pregnancy outcome in patients with recurrent miscarriage subsequent to a firstborn boy

Henriette Svarre Nielsen*, Rudi Steffensen, Kim Varming, Astrid G. S. Van Halteren, Eric Spierings, Lars P. Ryder, Els Goulmy, Ole Bjarne Christiansen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

59 Citations (Scopus)

Abstract

Healthy females, pregnant with a boy, generate immune responses against male-specific minor histocompatibility (HY) antigens. The clinical importance of these responses is evident in stem cell transplantation. Birth of a boy prior to a series of miscarriages reduces the chance of a subsequent live birth. This study explores the putative impact of known HY-presenting HLA alleles on future pregnancy outcome in women with at least three consecutive miscarriages following a birth [secondary recurrent miscarriage (SRM)]. HLA-A, -B, -DRB1, DRB3-5 and DQB1 genotyping was performed in 358 SRM patients and in 203 of their children born prior to the miscarriages. The subsequent live birth in women with boys prior to the miscarriages compared with girls is lower in women with HY-restricting HLA class II alleles [odds ratio (OR): 0.17 (0.1-0.4), P = 0.0001]. One HY-restricting HLA class II allele in women with firstborn boys significantly reduces the chances of a live birth [OR: 0.46 (0.2-0.9), P = 0.02]. Two HY-restricting HLA class II alleles further reduced this chance [OR: 0.21 (0.1-0.7), P = 0.02]. HY-restricting HLA class II did not reduce the chances of a live birth in SRM women with firstborn girls. HY-restricting HLA class II alleles are associated with a decreased chance of a live birth in SRM women with firstborn boys. These findings strongly indicate an aberrant maternal immune reaction against fetal HY-antigens in SRM. The results may shed light on the as-yet unknown immunological causes of SRM and may help understand the successful maternal acceptance of the fetal semi-allograft.

Original languageEnglish
Pages (from-to)1684-1691
Number of pages8
JournalHuman Molecular Genetics
Volume18
Issue number9
DOIs
Publication statusPublished - 1-May-2009

Keywords

  • VERSUS-HOST-DISEASE
  • MINOR HISTOCOMPATIBILITY ANTIGENS
  • STEM-CELL TRANSPLANTATION
  • PLASMA FETAL DNA
  • RISK-FACTORS
  • GROWTH RESTRICTION
  • BONE-MARROW
  • T-CELLS
  • PREECLAMPSIA
  • IMPACT

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