MATERNAL HLA CLASS-II ALLOGENOTYPES ARE MARKERS FOR THE PREDISPOSITION TO FETAL LOSSES IN FAMILIES OF WOMEN WITH UNEXPLAINED RECURRENT FETAL LOSS

The HLA allogenotypes DR1/Br, DR3 and DR10 (entitled risk HLA markers) have been reported as being genetic markers for the predisposition to experience unexplained recurrent fetal losses. The aim of the study was to determine whether the putative risk HLA markers might also be markers for the risk of pregnancy loss in sisters and wives of brothers of women with unexplained recurrent fetal losses. Information concerning pregnancy outcomes among the relatives of 146 consecutive women with unexplained recurrent fetal losses was collected. Ninety-five of the full sisters, 69 of the full brothers and 50 of the wives of the brothers were HLA typed. Sisters who had experienced at least one previous pregnancy loss (affected women) shared more HLA haplotypes with the proband than unaffected sisters, when the proband was positive for the risk markers (P = 0.02). More affected than unaffected sisters and brothers' wives were positive for the risk markers (P < 0.005 and P < 0.03; respectively). The lowest estimate of the odds ratio for experiencing pregnancy loss among sisters and brothers' wives who were positive compared with those negative for the risk markers was 3.5 (95% credible interval = 1.9-5.8). It is concluded that maternal DR1/Br, DR3 and DR10 allogenotypes seem to be genetic markers for the risk of pregnancy loss among relatives of women with unexplained recurrent fetal losses. The pattern of inheritance suggests a polygenic mode of inheritance with alleles linked to the risk HLA markers interacting with non-HLA linked genes expressed on the fetus or the trophoblast.