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 mech anisms is responsible for recurrent spontaneous abortions (RSA), mater nal class Il HLA antigens might be expected to be involved. We wanted to evaluate the impact of these antigens on pregnancy outcome in RSA w omen 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 t he next pregnancy in 94 patients. Sisters, brothers, and wives of brot hers of 146 consecutive patients were HLA typed and their pregnancy ou tcomes were correlated to the HLA-DR types. RESULTS: HLA-DR1/Br and -D R3 were each significantly increased in women with at least four previ ous pregnancy losses (both P-values < 0.05 after correction for multip le comparisons). In the prospective study, 62% of the HLA-DR1/Br and/o r -DR3 positive patients miscarried the next pregnancy compared with o nly 29% of those negative for both allogenotypes (P = 0.025). The fami ly studies indicated that female relatives of RSA patients had a great er 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 allog enotypes. CONCLUSIONS: Maternal HLA-DR allogenotypes DR1/Br and -DR3 o r closely linked genes seem to predispose to pregnancy losses in RSA p atients and their first degree relatives.