Maternal HLA class II alleles predispose to pregnancy losses in Danish women with recurrent spontaneous abortions and their female relatives.

PROBLEM

If damage to the trophoblast mediated through autoimmune mechanisms is responsible for recurrent spontaneous abortions (RSA), maternal class II HLA antigens might be expected to be involved. We wanted to evaluate the impact of these antigens on pregnancy outcome in RSA women and their relatives.

METHOD

HLA-DR and -DQ typing using RFLP and PCR-SSP methods was carried out in 234 Danish women with unexplained RSA and 360 controls. The HLA-DR types were correlated to outcome of the next pregnancy in 94 patients. Sisters, brothers, and wives of brothers of 146 consecutive patients were HLA typed and their pregnancy outcomes were correlated to the HLA-DR types.

RESULTS

HLA-DR1/Br and -DR3 were each significantly increased in women with at least four previous pregnancy losses (both P-values < 0.05 after correction for multiple comparisons). In the prospective study, 62% of the HLA-DR1/Br and/or -DR3 positive patients miscarried the next pregnancy compared with only 29% of those negative for both allogenotypes (P = 0.025). The family studies indicated that female relatives of RSA patients had a greater risk (odds ratio = 5.0, 95% CI = 2.0-11.0) of pregnancy losses when positive for HLA-DR1/Br and/or -DR3 than those negative for the allogenotypes.

CONCLUSIONS

Maternal HLA-DR allogenotypes DR1/Br and -DR3 or closely linked genes seem to predispose to pregnancy losses in RSA patients and their first degree relatives.