Frequency and clinical relevance of anti-cyclic citrullinated peptide antibody in idiopathic interstitial pneumonias.

Abstract

Although anti-cyclic citrullinated peptide antibody (ACPA) is highly specific for rheumatoid arthritis (RA), some patients with idiopathic interstitial pneumonia (IIP) are ACPA-positive, but do not fulfill the diagnostic criteria for RA. The clinical significance of ACPA in such patients is as yet unclear. We aimed to investigate the frequency of ACPA positivity and its clinical significance in patients initially diagnosed with IIP. We retrospectively analyzed 370 consecutive patients who were diagnosed with IIP and for whom serum ACPA results were available. The incidence of ACPA positivity and its predictive role for subsequent onset of RA was examined. Risk factors for development of RA were evaluated by Cox hazards analysis. Of 370 patients, 24 (6.5%) were ACPA-positive, including 7 of 144 patients (4.9%) initially diagnosed with idiopathic pulmonary fibrosis (IPF) and 17 of 226 patients (7.5%) with non-IPF. The cumulative 3-year incidence of overt RA was significantly higher in patients who were positive rather than negative for ACPA (28.9% vs. 1.1%, P < 0.01). On multivariate analysis, younger age was independently associated with development of RA in patients who were ACPA-positive (per one year increase: hazard ratio = 0.93, 95% confidence interval 0.87-0.99, P = 0.03). Among patients initially diagnosed with IIP, a small proportion was positive for ACPA, of whom approximately one-third subsequently developed RA within 3 years from IIP diagnosis. Clinicians should be alert to the possibility of RA developing in patients with IIP who are ACPA-positive, particularly those patients who are younger.