Increased frequency of HLA-DR4 allele in women with unexplained recurrent spontaneous abortions, detected by the method of PCR-SSP.

We investigated whether HLA-DR genes are associated with the etiology of unexplained recurrent spontaneous abortion (URSA), by using the polymerase chain reaction-sequence-specific primers (PCR-SSP) method, which is more accurate than serological typing. In women (n = 27) who experienced three or more consecutive spontaneous abortions in the first trimester, the frequency of the DR4 allele was significantly increased (relative risk = 4.25, P = 0.020) when compared with controls (n = 22) who experienced two or more full-term deliveries and no miscarriage. After high-resolutional analysis by a second PCR-SSP in positive cases for the DR4 allele phenotypic frequencies of HLA-DRB1*04 sub-alleles were disclosed. The most frequent sub-allele was DRB1*0405, followed by DRB1*0406 in both women with URSA and controls. However, none of the specific sub-alleles were attributed statistically to the increase in the DR4 allele in women with URSA.