HLA-DRB1*0404 is strongly associated with anticalpastatin antibodies in rheumatoid arthritis
HLA-DRB1*0404 is strongly associated with anticalpastatin antibodies in rheumatoid arthritis
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DOI：
10.1136/ard.2006.067231
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发表时间：
2007-12-01
影响因子：
27.4
通讯作者：
Roudier, Jean
中科院分区：
文献类型：
--
作者：
Auger, Isabelle;Roudier, Chantal;Roudier, Jean
目的：为了测试HLA-DR等位基因是否影响类风湿关节炎（RA）患者特定自身抗体的产生，我们通过使用2D印迹，用不同HLA-DR等位基因纯合的RA患者血清筛选滑膜蛋白。我们发现，RA患者的血清HLA-DRB 1 * 0404纯合子识别一个100 kDa的滑膜蛋白被鉴定为calpastatin。我们研究了钙蛋白酶抑制素上的B和T细胞表位及其与HLA-DRB 1 * 0404的相关性。方法：使用纯化的滑液钙蛋白酶抑制素或包含整个钙蛋白酶抑制素蛋白的钙蛋白酶抑制素肽作为免疫吸附剂，通过内部ELISA计算表达不同RA相关HLA-DR等位基因组合的患者中阳性血清的频率。钙蛋白酶抑制蛋白肽与HLA-DR等位基因之间的相互作用通过直接结合试验进行测试。结果：我们发现RA相关的HLA-DR等位基因与RA患者血清中抗滑膜钙蛋白酶抑制蛋白自身抗体的存在相关。HLA-DRB 1 * 0404与RA血清中的抗滑膜钙蛋白酶抑制素密切相关。一个线性B细胞表位优先与HLA-DRB 1 * 0404相关。来自钙蛋白酶抑制素的多个肽结合每个测试的与RA相关或不相关的HLA-DR等位基因。来自钙蛋白酶抑制素的结构域1和4的肽是最好的HLA-DR等位基因结合剂。T细胞对钙蛋白酶抑制素的反应在RA患者中是频繁的，并且独立于HLA-DR background.Conclusions：HLA-DRB 1 * 0404与类风湿关节炎中的抗钙蛋白酶抑制素抗体密切相关。
Objective: To test whether HLA-DR alleles influence the production of particular autoantibodies in rheumatoid arthritis ( RA) patients, we screened synovial proteins with sera of RA patients homozygous for different HLA-DR alleles by using 2D blots. We found that sera of RA patients homozygous for HLA-DRB1* 0404 recognised a 100-kDa synovial protein identified as calpastatin. We studied B and T cell epitopes on calpastatin and their association with HLA-DRB1* 0404.Methods: The frequency of positive sera in patients expressing different RA-associated HLA-DR allele combinations was calculated by inhouse ELISA using purified synovial calpastatin or calpastatin peptides encompassing the entire calpastatin protein as immunosorbent. Interaction between calpastatin peptides and HLA-DR alleles was tested by a direct binding assay. T cell responses to calpastatin were measured in RA patients and controls.Results: We found that RA-associated HLA-DR alleles are associated with presence of autoantibodies to synovial calpastatin in RA patients' sera. HLA-DRB1* 0404 is strongly associated with antisynovial calpastatin in RA sera. One linear B cell epitope is preferentially associated with HLA-DRB1* 0404. Multiple peptides from calpastatin bind every tested HLA-DR allele associated or not with RA. Peptides from domain 1 and 4 of calpastatin are the best HLA-DR allele binders. The T cell response to calpastatin is frequent in RA patients and independent of the HLA-DR background.Conclusions: HLA-DRB1* 0404 is strongly associated with anticalpastatin antibodies in rheumatoid arthritis.