吸烟导致类风湿关节炎的机制有待进一步研究

作者:发布时间:2014/7/4 8:40:18
吸烟导致类风湿关节炎的机制有待进一步研究 
 杨麟 
        摘要目标:来自于北欧的类风湿性关节炎(RA)患者的数据表明基因与环境因素与类风湿关节炎的发病有很强的关联性。吸烟与HLA-DRB1基因扩展表位与抗瓜氨酸α烯醇化酶抗体和波形蛋白抗体有很强关联性。由于韩国人群的类风湿关节炎相关的HLA-DRB1等位基因的差异显著,因此我们进一步研究了在韩国人群中的抗环瓜氨酸肽/蛋白抗体的特异性。 
        方法:我们测定了513例患者的抗纤维蛋白原,α烯醇化酶和波形蛋白和抗环瓜氨酸肽(CCP)抗体。采用Mann-Whitney U检验用于比较抗体水平。Logistic回归产生的OR为1101对照的病例对照分析类风湿关节炎患者数据。Logistic回归分析患者抗环瓜氨酸肽/蛋白抗体的特异性和骨侵蚀。
         结果:抗纤维蛋白原,α烯醇化酶和波形蛋白和抗环瓜氨酸肽(CCP)抗体的特异性分别为74.7%,86.7%,63.9%和45.5%。抗环瓜氨酸肽/蛋白抗体的患者的数量的表达水平与HLA-DRB1基因扩展表位的表达水平密切相关。吸烟与抗α烯醇化酶抗体密切相关。然而,基因-环境相互作用与所有抗环瓜氨酸肽/蛋白抗体阳性组相关联,但最高相关性被认为是抗波形蛋白和抗环瓜氨酸肽亚群。在没有HLA-DRB1基因扩展表位的情况下,吸烟仅仅提高了抗CCP抗体阴性患者的风险。骨侵蚀的存在与抗环瓜氨酸肽/蛋白抗体的特异性不相关。
        结论:HLA-DRB1基因扩展表位与抗环瓜氨酸肽/蛋白抗体的特异性密切相关,但吸烟增加抗环瓜氨酸肽/蛋白抗体的特异性的证据不足。 
        附原文:Abstract OBJECTIVES: Data from North European rheumatoid arthritis (RA) populations has suggested a particularly strong association of gene-environment interaction between smoking and HLA-DRB1 shared epitope (SE) with antibodies to citrullinated α-enolase (CEP-1) and vimentin (cVim) peptides. We investigated this further by examining anticitrullinated peptide/protein antibody (ACPA) fine specificity in a Korean cohort, where there are notable differences in the RA-associated HLA-DRB1 alleles.METHODS:Antibodies to fibrinogen (cFib), α-enolase (CEP-1) and vimentin (cVim) peptides and cyclic citrullinated peptide (CCP) were measured in 513 cases. The Mann-Whitney U test was used to compare antibody levels. Logistic regression generated ORs for RA in a case-control analysis with 1101 controls. Association of ACPA status and erosion in patients with RA was examined by logistic regression.RESULTS:Anti-CCP, CEP-1, cVim and fibrinogen peptides were found in 86.7%, 63.9%, 45.5% and 74.7%, respectively. The number of ACPA and their levels were associated with SE, with evidence of a gene-dosage effect. There was a particular association of smoking with levels of anti-CEP-1. However, a gene-environment interaction was associated with all the ACPA positive subgroups, albeit the highest OR was seen with the anti-CCP+/cVim+ subset. In the absence of SE, smoking only conferred risk for anti-CCP negative subsets. The presence of erosions was not associated with the number of positive ACPA or specificity.CONCLUSIONS:The SE governed the magnitude and diversity of the ACPA response, but its interaction with smoking did not exclusively segregate with any of the ACPA specificities studied here. Smoking was associated with RA by SE-dependent and independent effects. 
引自:Fisher BA, Bang SY, Chowdhury M, Lee HS, Kim JH, Charles P, Venables P, Bae SC. Smoking, the HLA-DRB1 shared epitope and ACPA fine-specificity in Koreans with rheumatoid arthritis: evidence for more than one pathogenic pathway linking smoking to disease. Ann Rheum Dis. 2014 Apr;73(4):741-7. doi: 10.1136/annrheumdis-2012-202535. Epub 2013 Mar 16. 
原文链接:http://www.ncbi.nlm.nih.gov/pubmed/23505239