Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced amelioration of rheumatoid arthritis

N Engl J Med. 1993 Aug 12;329(7):466-71. doi: 10.1056/NEJM199308123290704.


Background: Rheumatoid arthritis frequently remits during pregnancy, for unknown reasons. Since an immune response to paternally inherited fetal HLA can occur during normal pregnancy and since rheumatoid arthritis is an autoimmune disorder with a known HLA class II antigen association, we tested the hypothesis that maternal-fetal disparity in HLA alloantigens might be associated with the pregnancy-induced remission of rheumatoid arthritis.

Methods: We studied 57 pregnancies of 41 women with rheumatoid arthritis, 18 prospectively and 39 retrospectively. Serologic and DNA techniques were used to study HLA class I and II antigens. For newborns, typing was performed from cord-blood samples obtained at delivery. For four young children, typing was performed from DNA extracted from hair samples.

Results: We found significantly more maternal-fetal disparity in HLA-DR and DQ antigens in pregnancies characterized by the remission or improvement of rheumatoid arthritis than in pregnancies characterized by active disease. Further studies using DNA-typing techniques to define allelic variants of HLA-DR and DQ antigens 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 pregnancies 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 arthritis during pregnancy is associated with a disparity in HLA class II antigens between mother and fetus. These findings suggest that the maternal immune response to paternal HLA antigens may have a role in the pregnancy-induced remission of rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alleles
  • Arthritis, Rheumatoid / immunology*
  • DNA
  • Female
  • Fetal Blood / immunology
  • Fetus / immunology*
  • HLA Antigens / blood
  • HLA Antigens / genetics
  • HLA-DQ Antigens / blood
  • HLA-DQ Antigens / genetics
  • HLA-DR Antigens / blood
  • HLA-DR Antigens / genetics
  • Histocompatibility Antigens Class II / blood*
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • Infant, Newborn
  • Isoantigens / immunology
  • Odds Ratio
  • Pregnancy
  • Pregnancy Complications / immunology*
  • Prospective Studies
  • Retrospective Studies


  • HLA Antigens
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Histocompatibility Antigens Class II
  • Isoantigens
  • DNA