title: Rheumatoid arthritis in the Women's Health Initiative: methods and baseline evaluation.
abstract: Second-generation assays for anti-cyclic citrullinated peptide (anti-CCP), a highly sensitive and specific marker for rheumatoid arthritis (RA), have redefined the epidemiology of RA. In the Women's Health Initiative (WHI) RA study (2009-2011), we evaluated the prevalence of anti-CCP positivity among 15,691 (10.2% of 161,808) WHI participants aged 50-79 years who reported RA. Using stored baseline specimens, we measured serum anti-CCP, rheumatoid factor (RF), and antinuclear antibody in a defined sample of 9,988 of black, white, and Hispanic women. In a subset of women, we measured plasma cytokine levels and number of copies of the human leukocyte antigen (HLA)-DRB1 (HLA-DRB1) shared epitope in DNA by means of Luminex polymerase chain reaction typing (Luminex Corporation, Austin, Texas). We validated classification of probable clinical RA in 2 clinics as anti-CCP positivity or self-reported validated use of disease-modifying antirheumatic drugs (DMARDs). The prevalence of anti-CCP positivity was 8.1%, and the prevalence of RF positivity was approximately 16.0%. DMARD use including prednisone was reported by 1,140 (11.4%) participants (841 excluding prednisone) but by 57.5% of anti-CCP-positive women. The prevalence of 2 shared epitopes was also much higher for anti-CCP-positive women (18.2%, as opposed to only 5.5% for women with anti-CCP-negative DMARD-positive RA and 6.6% for anti-CCP-negative, RF-negative DMARD nonusers). Median cytokine levels were much higher for anti-CCP-positive/RF-positive women. Women with anti-CCP-positive RA and anti-CCP-negative RA had different characteristics with regard to HLA shared epitope, cigarette smoking, and inflammation (cytokines).
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Rachel H
authors.initials: RH
authors.lastname: Mackey
authors.forename: Brian T
authors.initials: BT
authors.lastname: Walitt
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Deane
authors.forename: V Michael
authors.initials: VM
authors.lastname: Holers
authors.forename: William H
authors.initials: WH
authors.lastname: Robinson
authors.forename: Jeremy
authors.initials: J
authors.lastname: Sokolove
authors.forename: Yuefang
authors.initials: Y
authors.lastname: Chang
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
mesh_terms: D000368:Aged; D000974:Antibodies, Antinuclear / Q000097:blood; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D015415:Biomarkers / Q000097:blood; D016207:Cytokines / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000097:blood; D006801:Humans; D007155:Immunologic Factors / Q000097:blood; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000097:blood* / Q000276:immunology; D016133:Polymerase Chain Reaction; D012217:Rheumatoid Factor / Q000097:blood*; D016036:Seroepidemiologic Studies; D014481:United States / Q000453:epidemiology; D016387:Women's Health / Q000706:statistics & numerical data*
chemical_list: D000974:Antibodies, Antinuclear; D018501:Antirheumatic Agents; D015415:Biomarkers; D016207:Cytokines; D059811:HLA-DRB1 Chains; D007155:Immunologic Factors; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
keywords: cytokines; epidemiologic methods; genetics; rheumatoid arthritis