Clinical and radiological distinctiveness of anti-cyclic citrullinated peptide antibody-negative rheumatoid arthritis-associated interstitial lung disease: a retrospective cohort study

OBJECTIVE: This study aimed to investigate the differences in clinical manifestations, serological profiles, pulmonary function, and high-resolution computed tomography (HRCT) findings between patients with anti-cyclic citrullinated peptide (CCP) antibody-negative and anti-CCP-positive rheumatoid arthritis-associated interstitial lung disease (RA-ILD). METHOD: A retrospective cohort of 214 RA-ILD patients admitted to Peking University Third Hospital between December 2009 and May 2025 was analysed. Comprehensive clinical data, laboratory parameters, pulmonary function tests, and HRCT features were systematically compared between anti-CCP-negative and anti-CCP-positive groups. RESULTS: Among the 214 RA-ILD patients, 41 (19.2%) were anti-CCP negative and 173 (80.8%) were anti-CCP positive. Compared with the anti-CCP-positive group, the anti-CCP-negative group had a lower proportion of males (17.1% vs 36.4%, p < 0.05) and smokers (12.2% vs 28.3%, p < 0.05), but a higher prevalence of anti-SSB antibody positivity (10.8% vs 2.5%, p < 0.05). HRCT revealed fewer fibrotic features, including reticulation, honeycombing, and traction bronchiectasis (36.6% vs 67.1%, p < 0.05), and a lower prevalence of the usual interstitial pneumonia pattern (22.0% vs 43.4%, p < 0.05) in the anti-CCP-negative group. No significant intergroup differences were observed in age at RA onset, comorbidities, disease activity scores, velcro rales, or pulmonary function parameters. CONCLUSION: While anti-CCP-negative and anti-CCP-positive RA-ILD patients share many clinical similarities, the anti-CCP-negative subgroup is characterized by a distinct profile including lower frequencies of males and smoking, higher anti-SSB antibody positivity, and less severe fibrotic lesions on HRCT.