一种前瞻性的方法来调查临床前类风湿关节炎(RA)的自然历史,使用RA先证者的一级亲属。

Jason R Kolfenbach, Kevin D Deane, Lezlie A Derber, Colin O'Donnell, Michael H Weisman, Jane H Buckner, Vivian H Gersuk, Shan Wei, Ted R Mikuls, James O'Dell, Peter K Gregersen, Richard M Keating, Jill M Norris, V Michael Holers
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引用次数: 148

摘要

目的:描述一项针对类风湿性关节炎(RA)先证患者一级亲属(FDRs)的大型多中心前瞻性队列研究,并概述该研究在调查RA发展自然史中的应用。方法:共有1058名fdr被纳入一项前瞻性研究,调查遗传和环境对RA相关自身免疫发展的影响,这些患者均不符合美国风湿病学会的RA标准。对这些fdr的人口统计学、流行病学、遗传学、自身抗体和体格检查数据进行了描述,并研究了遗传因素、自身抗体、炎症和关节疾病之间的关系。结果:55%的fdr具有>或=1个共享表位拷贝,20%具有>或=1个PTPN22多态性拷贝,约16%的fdr类风湿因子(RF;包括同型)和/或抗环瓜氨酸肽抗体。IgM-RF阳性与检查中>或=1个压痛关节相关(优势比[or] 2.50, 95%可信区间[95% CI] 1.27-4.89;P < 0.01)和c反应蛋白(CRP)水平升高(OR 5.31, 95% CI 1.45-19.52;P = 0.01)。结论:未患RA的fdr患者存在较高的遗传危险因素和RA相关自身抗体。此外,RF与关节触痛和CRP水平升高相关,表明自身抗体是该队列中ra相关自身免疫的有效中间标记物。这个前瞻性的FDR队列将是评估遗传和流行病学因素与ra相关自身免疫发展之间关系的宝贵资源。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA.

A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA.

Objective: To describe a large, multicenter prospective cohort study of first-degree relatives (FDRs) of probands with rheumatoid arthritis (RA), and outline the use of such a study in investigating the natural history of RA development.

Methods: A total of 1,058 FDRs, none of whom met the American College of Rheumatology criteria for RA, were enrolled in a prospective study investigating genetic and environmental influences on the development of RA-related autoimmunity. Demographic, epidemiologic, genetic, autoantibody, and physical examination data from the initial study enrollment visit were described for these FDRs, and the relationship was examined between genetic factors, autoantibodies, inflammation, and joint disease.

Results: Fifty-five percent of the FDRs had > or =1 copy of the shared epitope, 20% had > or =1 copy of the PTPN22 polymorphism, and approximately 16% were positive for rheumatoid factor (RF; including isotypes) and/or anti-cyclic citrullinated peptide antibody. IgM-RF positivity is associated with > or =1 tender joint on examination (odds ratio [OR] 2.50, 95% confidence interval [95% CI] 1.27-4.89; P < 0.01) and elevated C-reactive protein (CRP) levels (OR 5.31, 95% CI 1.45-19.52; P = 0.01).

Conclusion: FDRs without RA demonstrate high prevalences of genetic risk factors and RA-related autoantibodies. Additionally, an RF association with tender joints and elevated CRP levels suggests that autoantibodies are a valid intermediate marker of RA-related autoimmunity in this cohort. This prospective FDR cohort will be a valuable resource for evaluating the relationship between genetic and epidemiologic factors and the development of RA-related autoimmunity.

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来源期刊
Arthritis and rheumatism
Arthritis and rheumatism 医学-风湿病学
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