MATERNAL-FETAL DISPARITY IN HLA CLASS-II ALLOANTIGENS AND THE PREGNANCY-INDUCED AMELIORATION OF RHEUMATOID-ARTHRITIS
MATERNAL-FETAL DISPARITY IN HLA CLASS-II ALLOANTIGENS AND THE PREGNANCY-INDUCED AMELIORATION OF RHEUMATOID-ARTHRITIS
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DOI：
10.1056/nejm199308123290704
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发表时间：
1993-08-12
影响因子：
158.5
通讯作者：
HANSEN, JA
中科院分区：
文献类型：
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作者：
NELSON, JL;HUGHES, KA;HANSEN, JA
背景风湿性关节炎经常在怀孕期间缓解，原因不明。由于在正常妊娠期间可以发生对父系遗传的胎儿HLA的免疫应答，并且由于类风湿性关节炎是一种具有已知HLA II类抗原关联的自身免疫性疾病，因此我们测试了HLA同种异体抗原的母胎差异可能与妊娠诱导的类风湿性关节炎缓解相关的假设。我们研究了41例类风湿性关节炎患者的57例妊娠，其中18例前瞻性研究，39例回顾性研究。血清学和DNA技术用于研究HLA I类和II类抗原。对于新生儿，从分娩时获得的脐带血样本进行分型。对于四个年幼的孩子，分型进行从头发样本中提取的DNA。我们发现，与活动性疾病的孕妇相比，类风湿性关节炎缓解或改善的孕妇HLA-DR和DQ抗原的母胎差异更大。使用DNA分型技术来确定HLA-DR和DQ抗原的等位基因变体的进一步研究证实了这一观察结果。34例妊娠中有26例（76%）的HLA-DRB 1、DQA和DQB等位基因发生母胎差异，而12例妊娠中有3例（25%）的HLA-DRB 1、DQA和DQB等位基因发生母胎差异（比值比，9.7; P = 0.003）。HLA-DQA等位基因在两组间的差异最为显著。妊娠期类风湿性关节炎的改善与母亲和胎儿之间HLA II类抗原的差异有关。这些研究结果表明，母亲对父亲HLA抗原的免疫反应可能在妊娠诱导的类风湿关节炎缓解中发挥作用。
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.