HLA class II alleles confer susceptibility to recurrent fetal losses in Danish women.

HLA-DR and -DQ typings were performed by a combination of RFLP and PCR-SSP techniques in 234 Danish women with at least three consecutive unexplained fetal losses (recurrent fetal losses) and 360 controls and the DRB1, DQA1 and DQB1 alleles were deduced. In the total group of patients, the frequency of no DRB1-DQA1-DQB1 haplotype was significantly increased compared with controls. In the subgroup of 97 women with four or more fetal losses (multiple fetal loss group), the frequency of women carrying the DRB10101, DQA10101, DQB10501; DRB10102, DQA10101, DQB10501 and DRB10103, DQA10101, DQB10501 haplotypes or the DRB10301, DQA10501, DQB10201 haplotype were significantly increased compared with controls (RR = 2.1; pc < 0.05 with regard to former three haplotypes combined and RR = 2.2; pc < 0.05 for the latter). The frequency of women with at least one of the four haplotypes was significantly (p < 0.002) increased with the number of previous fetal losses in the women's history. Analysis of the DQA1 and DQB1 phenotypes in women with at least four fetal losses showed that DQA10501 and DQB10501 were increased compared with controls (RR = 1.9; pc < 0.05 and RR = 2.2; pc < 0.025, respectively). Analysis of DRB1-DQA1-DQB1/DRB1-DQA1-DQB1 genotypes suggested that genotypes comprising both DQA10501 and DQB10501 alleles (in trans) exhibited a higher RR for experiencing at least four fetal losses (RR = 3.4, p = 0.002) than each of the alleles did alone.(ABSTRACT TRUNCATED AT 250 WORDS)