MATERNAL-FETAL DISPARITY IN HLA CLASS-II ALLOANTIGENS AND THE PREGNANCY-INDUCED AMELIORATION OF RHEUMATOID-ARTHRITIS

Background. Rheumatoid arthritis frequently remits during pregnancy, f or unknown reasons. Since an immune response to paternally inherited f etal HLA can occur during normal pregnancy and since rheumatoid arthri tis is an autoimmune disorder with a known HLA class II antigen associ ation, we tested the hypothesis that maternal-fetal disparity in HLA a lloantigens might be associated with the pregnancy-induced remission o f rheumatoid arthritis. Methods. We studied 57 pregnancies of 41 women with rheumatoid arthritis, 18 prospectively and 39 retrospectively. S erologic and DNA techniques were used to study HLA class I and II anti gens. For newborns, typing was performed from cord-blood samples obtai ned at delivery. For four young children, typing was performed from DN A extracted from hair samples. Results. We found significantly more ma ternal-fetal disparity in HLA-DR and DQ antigens in pregnancies charac terized by the remission or improvement of rheumatoid arthritis than i n pregnancies characterized by active disease. Further studies using D NA-typing techniques to define allelic variants of HLA-DR and DQ antig ens confirmed this observation. Maternal-fetal disparity in alleles of HLA-DRB1, DQA, and DQB occurred in 26 of 34 pregnancies characterized by remission or improvement (76 percent), as compared with 3 of 12 pr egnancies characterized by active arthritis (25 percent) (odds ratio, 9.7; P = 0.003). The difference between the two groups was most marked for alleles of HLA-DQA. Conclusions. Amelioration of rheumatoid arthr itis during pregnancy is associated with a disparity in HLA class II a ntigens between mother and fetus. These findings suggest that the mate rnal immune response to paternal HLA antigens may have a role in the p regnancy-induced remission of rheumatoid arthritis.