Kolfenbach Jason R, Deane Kevin D, Derber Lezlie A, O'Donnell Colin, Weisman Michael H, Buckner Jane H, Gersuk Vivian H, Wei Shan, Mikuls Ted R, O'Dell James, Gregersen Peter K, Keating Richard M, Norris Jill M, Holers V Michael
University of Colorado Denver, Aurora, CO, USA.
Arthritis Rheum. 2009 Dec 15;61(12):1735-42. doi: 10.1002/art.24833.
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.
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.
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).
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.
描述一项针对类风湿关节炎（RA）先证者一级亲属（FDR）的大型多中心前瞻性队列研究，并概述此类研究在调查RA发病自然史中的应用。
共有1058名FDR参与了一项前瞻性研究，这些人均未达到美国风湿病学会的RA诊断标准，该研究旨在调查遗传和环境因素对RA相关自身免疫性疾病发病的影响。对这些FDR在初次研究入组访视时的人口统计学、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。
55%的FDR有≥1份共享表位拷贝，20%有≥1份PTPN22多态性拷贝，约16%的类风湿因子（RF；包括各亚型）和/或抗环瓜氨酸肽抗体呈阳性。IgM-RF阳性与检查时≥1个压痛关节相关（比值比[OR]2.50，95%置信区间[95%CI]1.27 - 4.89；P < 0.01），且与C反应蛋白（CRP）水平升高相关（OR 5.31，95%CI 1.45 - 19.52；P = 0.01）。
无RA的FDR显示出遗传危险因素和RA相关自身抗体的高患病率。此外，RF与压痛关节及CRP水平升高之间的关联表明，自身抗体是该队列中RA相关自身免疫性疾病的有效中间标志物。这个前瞻性FDR队列将成为评估遗传和流行病学因素与RA相关自身免疫性疾病发病关系的宝贵资源。
