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278: Maternal-fetal HLA relationships at DRB loci in preeclampsia

      Objective

      Normal pregnancy depends on maternal tolerance of the semi-allogeneic fetus. Preeclampsia (PE) may reflect impaired maternal tolerance of the fetus. We sought to investigate whether maternal-fetal HLA relationships at Class II DRB loci are altered in PE. In addition to the DRB1 locus, we aimed to evaluate the supertypic DRB loci DRB3, DRB4, and DRB5, which represent evolutionary HLA lineages.

      Study Design

      Women meeting ACOG/NHLBI criteria for PE were recruited at diagnosis. Maternal peripheral and cord blood was collected. DNA was extracted by standard techniques. HLA genotyping was performed using a polymerase chain reaction/sequence-specific oligonucleotide probe technique for DRB1. Genotype for the DRB loci, DRB3, DRB4, or DRB5 was inferred based on known tight linkage disequilibrium with DRB1.

      Results

      Maternal-fetal relationships at the DRB1 locus and at the DRB3, DRB4, and DRB5 loci were classified as incompatible, bidirectionally compatible, or unidirectionally compatible from the maternal or fetal perspective. There was no difference in the distribution of classifications between patients with PE (n=33) and controls (n=365) (overall compatibility at DRB1 35.5% and 34.4%, and at DRB345 78.1% and 81.6%, respectively). Analyses of homozygosity at DRB1 and DRB345 showed a trend toward decreased homozygosity at DRB345 in PE (15.2% vs 25.8% in controls, p=0.17). Supertypic genotypic classification suggested a trend toward increased prevalence of haplotypes that lack an HLA Class II supertype, i.e. homozygous or heterozygous null (39.4% in preeclampsia vs 29.1% in controls, p=0.32).

      Conclusion

      Preliminary results do not suggest excessive maternal-fetal HLA sharing at DRB loci in PE. However, haplotype analysis according to DRB3, DRB4, DRB5, or null supertypic groups suggests a potential role that merits further investigation.