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OBJECTIVE: To evaluate the prevalence and predictive value of anti-cyclic citrullinated peptide (anti-CCP) antibodies in individuals who subsequently developed rheumatoid arthritis (RA) and to determine the relationship to rheumatoid factor (RF) of any isotype. METHODS: A case-control study was nested within the Northern Sweden Health and Disease Study and the Maternity cohorts of Northern Sweden. Patients with RA were identified among blood donors whose samples had been taken years before the onset of symptoms. Control subjects matched for age, sex, date of sampling, and residential area were selected randomly from the same cohorts. Anti-CCP antibody and RFs were determined using enzyme immunoassays. RESULTS: Eighty-three individuals with RA were identified as having donated blood before presenting with any symptoms of joint disease (median 2.5 years [interquartile range 1.1-4.7] before RA). In samples obtained before the onset of RA, the prevalence of autoantibodies was 33.7% for anti-CCP, 16.9% for IgG-RF, 19.3% for IgM-RF, and 33.7% for IgA-RF (all highly significant compared with controls). The sensitivities for detecting these autoantibodies >1.5 years and