Background Rheumatoid arthritis frequently remits during pregnancy,for unknown reasons. Since an immune response to paternallyinherited fetal HLA can occur during normal pregnancy and sincerheumatoid arthritis is an autoimmune disorder with a knownHLA class II antigen association, we tested the hypothesis thatmaternal-fetal disparity in HLA alloantigens might be associatedwith the pregnancy-induced remission of rheumatoid arthritis.
Methods We studied 57 pregnancies of 41 women with rheumatoidarthritis, 18 prospectively and 39 retrospectively. Serologicand DNA techniques were used to study HLA class I and II antigens.For newborns, typing was performed from cord-blood samples obtainedat delivery. For four young children, typing was performed fromDNA extracted from hair samples.
Results We found significantly more maternal-fetal disparityin HLA-DR and DQ antigens in pregnancies characterized by theremission or improvement of rheumatoid arthritis than in pregnanciescharacterized by active disease. Further studies using DNA-typingtechniques to define allelic variants of HLA-DR and DQ antigensconfirmed this observation. Maternal-fetal disparity in allelesof HLA-DRB1, DQA, and DQB occurred in 26 of 34 pregnancies characterizedby remission or improvement (76 percent), as compared with 3of 12 pregnancies characterized by active arthritis (25 percent)(odds ratio, 9.7; P = 0.003). The difference between the twogroups was most marked for alleles of HLA-DQA.
Conclusions Amelioration of rheumatoid arthritis during pregnancyis associated with a disparity in HLA class II antigens betweenmother and fetus. These findings suggest that the maternal immuneresponse to paternal HLA antigens may have a role in the pregnancy-inducedremission of rheumatoid arthritis.
Source Information
From the Human Immunogenetics Program, Division of Clinical Research, Fred Hutchinson Cancer Research Center, 1124 Columbia St., Seattle, WA 98104, where reprint requests should be addressed to Dr. Nelson.
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