Open AccessA prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first‐degree relatives of probands with RA
Author(s) -
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
Publication year - 2009
Publication title -
arthritis care & research
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.24833
Subject(s) - medicine , rheumatoid factor , autoantibody , rheumatoid arthritis , prospective cohort study , first degree relatives , proband , cohort , family history , ptpn22 , immunology , rheumatology , arthritis , odds ratio , single nucleotide polymorphism , antibody , genotype , genetics , biology , gene , mutation
Abstract 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.