Effects of Aging on Rheumatoid Factor and Anticyclic Citrullinated Peptide Antibody Positivity in Patients With Rheumatoid Arthritis

Objective. We investigated the factors that affect rheumatoid factor (RF) and anticyclic citrullinated peptide antibody (anti-CCP) positivity in patients with rheumatoid arthritis (RA). Methods. The study included all consecutive patients with RA treated at Keio University Hospital between 2016 and 2017. We recorded age at diagnosis, sex, smoking habit, BMI (kg/m²), and family history, and investigated the association between these variables and RF and anti-CCP positivity. Results. We recruited 1685 patients with RA. The mean age at diagnosis was 51.9 years, and 83.4% of the patients were women. Positivity rates of RF and anti-CCP almost linearly decreased along with the increase in age at RA diagnosis (grouped by decade) after ≥ 30 years of age (RF: 80.5%, 84.2%, 81.1%, 78%, 74.6%, 62.6%, 51.4%, P < 0.001; anti-CCP: 79.9%, 87.4%, 81.7%, 74%, 70.5%, 60.2%, 37.1%; P < 0.001). Multivariable analysis revealed that age was independently associated with seronegativity in women (RF: odds ratio [OR] 0.98, 95% CI 0.97-0.99, P < 0.001; anti-CCP: OR 0.97, 95% CI 0.96-0.98; P < 0.001), nonsmoking history (RF: OR 0.98, 95% CI 0.97-0.99, P < 0.001; anti-CCP: OR 0.97, 95% CI 0.96-0.98; P < 0.001), and BMI < 25 (RF: OR 0.98, 95% CI 0.97-0.99; P < 0.001; anti-CCP: OR 0.97, 95% CI 0.97-0.98; P < 0.001). Conclusion. Aging is an independent contributor for seronegative RA in patients who are female, have a nonsmoking history, and a BMI < 25.