Association of maternal HLA haplotypes with recurrent spontaneous abortions

Histocompatibility typing was done on 63 women with idiopathic, recurrent abortions (greater than or equal to 3 consecutive, spontaneous abortions; summarized abortion rate: 92.8%), 112 of their full siblings and 101 parents. The distribution of full sisters sharing 2, 1 and 0 of the probands' haplotypes diverged from expected Mendelian segregation (p less than 0.05). Sisters sharing both the probands' haplotypes had an abortion rate of 59.1%, haploidentical sisters had an abortion rate of 25.0% whereas 6.3% of the pregnancies of the 0 haploidentical sisters had ended in miscarriage. The probands' HLA haplotypes included a significant (p less than 0.02) excess of HLA-A, B haplotypes which have previously been shown to exhibit features of positive linkage disequilibrium in Danes. Analysis of abortion rates among the probands and their siblings indicate that the idiopathic recurrent abortion syndrome and probably also the tendency to some sporadic abortions are inherited conditions determined by genes in the HLA region. The presented data may be compatible with an additive polygenic mode of inheritance with exclusive or predominant phenotypic expression in females controlled by an HLA linked spontaneous abortion susceptibility region (SASR).