TY - JOUR
T1 - A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA
AU - Kolfenbach, Jason R.
AU - Deane, Kevin D.
AU - Derber, Lezlie A.
AU - O'Donnell, Colin
AU - Weisman, Michael H.
AU - Buckner, Jane H.
AU - Gersuk, Vivian H.
AU - Wei, Shan
AU - Mikuls, Ted R.
AU - O'Dell, James
AU - Gregersen, Peter K.
AU - Keating, Richard M.
AU - Norris, Jill M.
AU - Holers, V. Michael
PY - 2009/12/15
Y1 - 2009/12/15
N2 - 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 ∼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.
AB - 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 ∼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.
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U2 - 10.1002/art.24833
DO - 10.1002/art.24833
M3 - Article
C2 - 19950324
AN - SCOPUS:73449140089
SN - 2151-4658
VL - 61
SP - 1735
EP - 1742
JO - Arthritis care & research
JF - Arthritis care & research
IS - 12
ER -