title: A prospective approach to investigating the natural history of preclinical rheumatoid arthritis (RA) using first-degree relatives of probands with RA.
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 > 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).
  
  
  CONCLUSIONS
  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.
authors: University of Colorado Denver, Aurora, CO, USA.
authors: Jason R
authors: JR
authors: Kolfenbach
authors: Kevin D
authors: KD
authors: Deane
authors: Lezlie A
authors: LA
authors: Derber
authors: Colin
authors: C
authors: O'Donnell
authors: Michael H
authors: MH
authors: Weisman
authors: Jane H
authors: JH
authors: Buckner
authors: Vivian H
authors: VH
authors: Gersuk
authors: Shan
authors: S
authors: Wei
authors: Ted R
authors: TR
authors: Mikuls
authors: James
authors: J
authors: O'Dell
authors: Peter K
authors: PK
authors: Gregersen
authors: Richard M
authors: RM
authors: Keating
authors: Jill M
authors: JM
authors: Norris
authors: V Michael
authors: VM
authors: Holers
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics; D012217:Rheumatoid Factor / Q000097:blood; D014481:United States / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein; D012217:Rheumatoid Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22