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巴西类风湿关节炎患者中的共同表位、瓜氨酸化环肽抗体与吸烟情况

Share epitope, citrullinated cyclic peptide antibodies and smoking in Brazilian rheumatoid arthritis patients.

作者信息

Oliveira Rene Donizeti, Junta Cristina Maria, Oliveira Fabíola Reis, Silva Lucienir Maria, Donadi Eduardo Antonio, Louzada-Junior Paulo

机构信息

Division of Clinical Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.

出版信息

Clin Rev Allergy Immunol. 2008 Feb;34(1):32-5. doi: 10.1007/s12016-007-8017-2.

DOI:10.1007/s12016-007-8017-2
PMID:18270855
Abstract

The events involved in the pathogenesis of rheumatoid arthritis (RA) still remain unclear, but certainly the etiology is multifactorial. Shared epitope (SE) of HLADRbeta1 is the most important genetic risk factor. Environmental risk factors are less understood. Smoking is a candidate, associated with the rising of citrullinated cyclic peptide antibodies (anti-CCP). Anti-CCP antibodies are highly specific for RA. In this study, we investigated whether the association between anti-CCP production and smoking was influenced by carriage of SE in a highly miscegenated population of patients with RA. One hundred Brazilian patients were inquired about cigarette smoking. For all of them, DNA for HLA typing and serum to anti-CCP antibodies quantification were obtained. Forty-two were smokers and 58 were nonsmokers. The SE was present in 61 patients and the anti-CCP was positive in 71 patients. We found that, among smokers, 25 were SE-positive, 22 presented with anti-CCP and 3 without anti-CCP, and 17 were SE-negative, 9 presented with anti-CCP and 8 without anti-CCP (OR 6.5, 95% CI 1.40 to 30.20). These results suggest that environmental factors contribute to the raising of anti-CCP in individuals with HLA background to RA, smoking being a strong candidate.

摘要

类风湿关节炎(RA)发病机制中涉及的事件仍不清楚,但病因肯定是多因素的。HLADRβ1的共享表位(SE)是最重要的遗传风险因素。环境风险因素的了解较少。吸烟是一个候选因素,与瓜氨酸化环肽抗体(抗CCP)的升高有关。抗CCP抗体对RA具有高度特异性。在本研究中,我们调查了在高度混血的RA患者群体中,抗CCP产生与吸烟之间的关联是否受SE携带情况的影响。询问了100名巴西患者的吸烟情况。为他们所有人获取了用于HLA分型的DNA和用于抗CCP抗体定量的血清。42人是吸烟者,58人是非吸烟者。61名患者存在SE,71名患者抗CCP呈阳性。我们发现,在吸烟者中,25人SE阳性,22人抗CCP阳性,3人抗CCP阴性,17人SE阴性,9人抗CCP阳性,8人抗CCP阴性(比值比6.5,95%置信区间1.40至30.20)。这些结果表明,环境因素促使具有RA HLA背景的个体中抗CCP升高,吸烟是一个有力的候选因素。

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Share epitope, citrullinated cyclic peptide antibodies and smoking in Brazilian rheumatoid arthritis patients.巴西类风湿关节炎患者中的共同表位、瓜氨酸化环肽抗体与吸烟情况
Clin Rev Allergy Immunol. 2008 Feb;34(1):32-5. doi: 10.1007/s12016-007-8017-2.
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Smoking increases rheumatoid arthritis susceptibility in individuals carrying the HLA-DRB1 shared epitope, regardless of rheumatoid factor or anti-cyclic citrullinated peptide antibody status.吸烟会增加携带HLA - DRB1共同表位的个体患类风湿性关节炎的易感性,无论其类风湿因子或抗环瓜氨酸肽抗体状态如何。
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Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis.人类白细胞抗原(HLA)II类基因与抗环瓜氨酸肽(CCP)自身抗体之间的关联会影响类风湿性关节炎的严重程度。
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本文引用的文献

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Smoking interacts with genetic risk factors in the development of rheumatoid arthritis among older Caucasian women.在老年白种女性类风湿关节炎的发病过程中,吸烟与遗传风险因素相互作用。
Ann Rheum Dis. 2006 Sep;65(9):1163-7. doi: 10.1136/ard.2005.049676. Epub 2006 Aug 3.
2
Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins.基于HLA - DRB1共享表位对瓜氨酸化蛋白抗体的特异性来优化复杂类风湿性关节炎的表型。
Arthritis Rheum. 2005 Nov;52(11):3433-8. doi: 10.1002/art.21385.
3
The devil in the details: the emerging role of anticitrulline autoimmunity in rheumatoid arthritis.
类风湿关节炎和慢性阻塞性肺疾病患者的循环抗环瓜氨酸肽抗体
Rheumatol Int. 2014 Jul;34(7):971-7. doi: 10.1007/s00296-013-2926-6. Epub 2013 Dec 24.
4
Autoimmune smoke and fire--coexisting rheumatoid arthritis and chronic obstructive pulmonary disease: a cross-sectional analysis.自身免疫性烟雾和火灾——同时存在的类风湿关节炎和慢性阻塞性肺疾病:一项横断面分析。
Immunol Res. 2013 Jul;56(2-3):261-6. doi: 10.1007/s12026-013-8395-x.
5
Association analysis of anti-Epstein-Barr nuclear antigen-1 antibodies, anti-cyclic citrullinated peptide antibodies, the shared epitope and smoking status in Brazilian patients with rheumatoid arthritis.巴西类风湿关节炎患者抗 EB 核抗原-1 抗体、抗环瓜氨酸肽抗体、共同表位与吸烟状况的关联分析。
Clinics (Sao Paulo). 2011;66(8):1401-6. doi: 10.1590/s1807-59322011000800016.
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The swollen joint, the thickened artery, and the smoking gun: tobacco exposure, citrullination and rheumatoid arthritis.肿胀的关节、增厚的动脉和冒烟的枪:烟草暴露、瓜氨酸化和类风湿关节炎。
Rheumatol Int. 2011 May;31(5):567-72. doi: 10.1007/s00296-010-1644-6. Epub 2010 Dec 7.
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Differential gene expression of peripheral blood mononuclear cells from rheumatoid arthritis patients may discriminate immunogenetic, pathogenic and treatment features.类风湿关节炎患者外周血单个核细胞的差异基因表达可能有助于区分免疫遗传学、发病机制及治疗特征。
Immunology. 2009 Jul;127(3):365-72. doi: 10.1111/j.1365-2567.2008.03005.x. Epub 2008 Dec 17.
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Clin Rev Allergy Immunol. 2008 Feb;34(1):1-3. doi: 10.1007/s12016-007-8014-5.
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J Immunol. 2005 Nov 1;175(9):5575-80. doi: 10.4049/jimmunol.175.9.5575.
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Ann Rheum Dis. 2006 Mar;65(3):366-71. doi: 10.1136/ard.2005.041079. Epub 2005 Jul 13.
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J Immunol. 2005 Apr 15;174(8):5057-64. doi: 10.4049/jimmunol.174.8.5057.
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Pathways to gene identification in rheumatoid arthritis: PTPN22 and beyond.类风湿关节炎中基因鉴定的途径:蛋白酪氨酸磷酸酶非受体型22及其他。
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The presence of citrullinated proteins is not specific for rheumatoid synovial tissue.瓜氨酸化蛋白的存在并非类风湿性滑膜组织所特有。
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A gene-environment interaction between smoking and shared epitope genes in HLA-DR provides a high risk of seropositive rheumatoid arthritis.吸烟与人类白细胞抗原DR(HLA-DR)中的共享表位基因之间的基因-环境相互作用会导致血清阳性类风湿性关节炎的高风险。
Arthritis Rheum. 2004 Oct;50(10):3085-92. doi: 10.1002/art.20553.
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Association between HLA class II genes and autoantibodies to cyclic citrullinated peptides (CCPs) influences the severity of rheumatoid arthritis.人类白细胞抗原(HLA)II类基因与抗环瓜氨酸肽(CCP)自身抗体之间的关联会影响类风湿性关节炎的严重程度。
Arthritis Rheum. 2004 Jul;50(7):2113-21. doi: 10.1002/art.20316.
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Citrullinated proteins: sparks that may ignite the fire in rheumatoid arthritis.瓜氨酸化蛋白:可能点燃类风湿性关节炎之火的火花。
Arthritis Res Ther. 2004;6(3):107-11. doi: 10.1186/ar1184. Epub 2004 Apr 19.