A Prospective Approach to Investigating the Natural History of Preclinical Rheumatoid Arthritis (RA) Using First-Degree Relatives of Probands With RA

作者：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^*

来源：Arthritis and Rheumatism, 2009, 61(12): 1735-1742.

DOI：10.1002/art.24833

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 >= 1 copy of the shared epitope, 20% had >= 1 copy of the PTPN22 polymorphism, and similar to 16% were positive for rheumatoid factor (RF; including isotypes) and/or anti-cyclic citrullinated peptide antibody. IgM-RF positivity is associated with >= 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.

• 出版日期2009-12-15
• 单位河北医科大学