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

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 Robert O'Dell, Peter K. Gregersen, Richard M. Keating, Jill M. Norris, V. Michael Holers

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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.

Original languageEnglish (US)
Pages (from-to)1735-1742
Number of pages8
JournalArthritis Care and Research
Volume61
Issue number12
DOIs
StatePublished - Dec 15 2009

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Rheumatoid Arthritis
Autoantibodies
Autoimmunity
C-Reactive Protein
Joints
Epidemiologic Factors
Odds Ratio
Prospective Studies
Confidence Intervals
Joint Diseases
Rheumatoid Factor
Physical Examination
Immunoglobulin M
Epitopes
Cohort Studies
Demography
Inflammation
Antibodies

ASJC Scopus subject areas

  • Rheumatology

Cite this

Kolfenbach, J. R., Deane, K. D., Derber, L. A., O'Donnell, C., Weisman, M. H., Buckner, J. H., ... Holers, V. M. (2009). A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA. Arthritis Care and Research, 61(12), 1735-1742. https://doi.org/10.1002/art.24833

A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA. / 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 Robert; Gregersen, Peter K.; Keating, Richard M.; Norris, Jill M.; Holers, V. Michael.

In: Arthritis Care and Research, Vol. 61, No. 12, 15.12.2009, p. 1735-1742.

Research output: Contribution to journalArticle

Kolfenbach, JR, Deane, KD, Derber, LA, O'Donnell, C, Weisman, MH, Buckner, JH, Gersuk, VH, Wei, S, Mikuls, TR, O'Dell, JR, Gregersen, PK, Keating, RM, Norris, JM & Holers, VM 2009, 'A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA', Arthritis Care and Research, vol. 61, no. 12, pp. 1735-1742. https://doi.org/10.1002/art.24833
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 Robert ; Gregersen, Peter K. ; Keating, Richard M. ; Norris, Jill M. ; Holers, V. Michael. / A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA. In: Arthritis Care and Research. 2009 ; Vol. 61, No. 12. pp. 1735-1742.
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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.",
author = "Kolfenbach, {Jason R.} and Deane, {Kevin D.} and Derber, {Lezlie A.} and Colin O'Donnell and Weisman, {Michael H.} and Buckner, {Jane H.} and Gersuk, {Vivian H.} and Shan Wei and Mikuls, {Ted R} and O'Dell, {James Robert} and Gregersen, {Peter K.} and Keating, {Richard M.} and Norris, {Jill M.} and Holers, {V. Michael}",
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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 Robert

AU - Gregersen, Peter K.

AU - Keating, Richard M.

AU - Norris, Jill M.

AU - Holers, V. Michael

PY - 2009/12/15

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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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