Identification of citrullinated eukaryotic translation initiation factor 4G1 as novel autoantigen in rheumatoid arthritis
Identification of citrullinated eukaryotic translation initiation factor 4G1 as novel autoantigen in rheumatoid arthritis
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DOI：
10.1016/j.bbrc.2005.12.160
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发表时间：
2006-03-03
影响因子：
3.1
通讯作者：
Yamamoto, K
中科院分区：
文献类型：
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作者：
Okazaki, Y;Suzuki, A;Yamamoto, K
针对瓜氨酸蛋白的抗体对类风湿性关节炎具有高度特异性。我们以前报道过编码4型缩氨酸脱亚胺酶基因的功能变异与类风湿关节炎密切相关。本研究的目的是研究类风湿关节炎患者血清样本所识别的瓜氨酸自身抗原。用PADI4对人软骨细胞表达文库进行瓜氨酸化，并用抗修饰瓜氨酸抗体和类风湿关节炎患者血清进行免疫筛选。分离到1个含有2480个碱基插入片段的免疫反应性cDNA克隆，序列分析表明，该克隆含有部分真核翻译起始因子4GL，对重组瓜氨酸化eIF4G1片段的免疫反应性在50.0%的RA患者中具有很高的特异性。抗瓜氨酸化eIF4G1抗体水平与抗CCP抗体水平相关。瓜氨酸化的eIF4G1是类风湿关节炎患者的候选瓜氨酸化自身抗原。因此，eIF4G1的瓜氨酸化可能参与了RA的发病过程。(C)2006 Elsevier Inc.保留所有权利。
Antibodies against citrullinated proteins are highly specific for rheumatoid arthritis. We previously reported that functional variants of the gene encoding peptidylarginine deiminase type 4 were closely associated with RA. The purpose of this study was to investigate the citrullinated autoantigens recognized by serum samples from patients with RA. The human chondrocyte cDNA expression library was citrullinated by PADI4 and was immunoscreened with anti-modified citrulline antibodies and sera from patients with rheumatoid arthritis. One immunoreactive cDNA clone containing a 2480-base pair insert was isolated and sequence analysis revealed that the cDNA included a part of the eukaryotic translation initiation factor 4GL Immunoreactivity against a recombinant citrullinated eIF4G1 fragment was observed with high specificity in 50.0% of RA patients. The levels of antibodies against citrullinated eIF4G1 were correlated with those of anti-CCP antibodies. Citrullinated eIF4G1 was identified as a candidate citrullinated autoantigen in RA patients. Citrullination of eIF4G1 may thus be involved in the pathogenesis of RA. (c) 2006 Elsevier Inc. All rights reserved.