Functional haplotypes of PADI4: relevance for rheumatoid arthritis specific synovial intracellular citrullinated proteins and anticitrullinated protein antibodies
Functional haplotypes of PADI4: relevance for rheumatoid arthritis specific synovial intracellular citrullinated proteins and anticitrullinated protein antibodies
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DOI：
10.1136/ard.2004.033548
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发表时间：
2005-09-01
影响因子：
27.4
通讯作者：
Baeten, D
中科院分区：
文献类型：
--
作者：
Cantaert, T;Coucke, P;Baeten, D
背景：在日本人群中，编码瓜氨酸酶的PADI4单倍型与类风湿性关节炎有关。目的：探讨PADI4单倍型、类风湿关节炎滑膜细胞内特异性瓜氨酸蛋白的存在与血清ACPA滴度的关系。免疫组织化学方法检测滑膜细胞内瓜氨酸蛋白的表达。用抗CCP2双抗体夹心法测定血清ACPA滴度。结果：PADI4单倍型频率、滑膜细胞内瓜氨酸蛋白和ACPA的存在与以往的研究结果基本一致。PADI4单倍型1或2与滑膜细胞内瓜氨酸蛋白的存在没有显著关联，尽管这些蛋白与较高的血清ACPA相关。PADI4单倍型与血清ACPA之间没有相关性，无论是用滴度进行连续分析，还是用诊断界值进行二分法分析。在单倍型1或2的纯合子或杂合子(1/2)中的进一步分析也未能显示PADI4多态与ACPA之间的关联。结论：滑膜细胞内瓜氨酸蛋白和ACPA之间的联系强调了滑膜蛋白的缺失在类风湿关节炎中的作用，但PADI4单倍型与这一自身免疫过程的生物学相关性是值得怀疑的，至少在欧洲人群中是这样。
Background: Haplotypes of PADI4, encoding for a citrullinating enzyme, were associated with rheumatoid arthritis in a Japanese population. It was suggested they were related to the presence of anticitrullinated protein antibodies ( ACPA).Objective: To explore the relation between PADI4 haplotypes, the presence of rheumatoid arthritis specific intracellular citrullinated proteins in synovial membrane, and serum ACPA titres.Methods: Synovial biopsies and peripheral blood samples were obtained in 59 patients with rheumatoid arthritis. Synovial intracellular citrullinated proteins were detected by immunohistochemistry. Serum ACPA titres were measured by anti-CCP2 ELISA. PADI4 haplotypes were determined by direct sequencing of the four exonic PADI4 single nucleotide polymorphisms.Results: PADI4 haplotype frequencies and the presence of synovial intracellular citrullinated proteins and ACPA were comparable with previous studies. There was no significant association between PADI4 haplotype 1 or 2 and the presence of synovial intracellular citrullinated proteins, although these proteins were associated with higher serum ACPA. There was no correlation between PADI4 haplotypes and serum ACPA, either by continuous analysis using the titres or by dichotomous analysis using the diagnostic cut off. Further analyses in homozygotes for haplotype 1 or 2 or in heterozygotes (1/2) also failed to show an association between PADI4 polymorphisms and ACPA. This contrasted with the clear association between ACPA levels and HLA-DR shared epitope.Conclusions: The link between synovial intracellular citrullinated proteins and ACPA emphasises the role of deimination of synovial proteins in rheumatoid arthritis, but the biological relevance of the PADI4 haplotypes for this autoimmune process is questionable, at least in a European population.