Serum anti-citrullinated protein antibodies and rheumatoid factor increase the risk of rheumatoid arthritis–related interstitial lung disease: a meta-analysis

• Published in: Clinical rheumatology 2021-11, Vol.40 (11), p.4533-4543
• Main Authors: Xie, Sisi, Li, Shu, Chen, Bilin, Zhu, Qing, Xu, Lichang, Li, Fen
• Format: Article
• Language: English
• Subjects: Antibodies; Autoantibodies; Citrulline; Lung diseases; Medicine; Medicine & Public Health; Meta-analysis; Original Article; Rheumatoid arthritis; Rheumatoid factor; Rheumatology; Sensitivity analysis
• ISSN: 0770-3198; 1434-9949
• DOI: 10.1007/s10067-021-05808-2

Background This meta-analysis aims to determine the association between antibodies including anti-citrullinated protein antibodies (ACPA) and rheumatoid factors (RF) and risk of rheumatoid arthritis–related interstitial lung disease (RA-ILD). Methods PubMed, Embase, and Cochrane were searched up to September 13, 2020, for studies investigating the risk of RA-ILD in ACPA-positive patients. The statistical meta-analysis and sensitivity analysis were performed using the Review Manager 5.4 and Stata16.0 software, respectively. Results Total 1 double-blind randomized controlled study and 16 observational studies, including 992 RA-ILD patients and 2223 RA-non ILD patients, met the inclusion criteria of the meta-analysis. Compared with ACPA-negative patients, positive serum ACPA increased the risk of RA-ILD (OR = 2.51; 95% CI: 1.35–4.68; P  = 0.004) and serum ACPA titer was significantly correlated with risk of RA-ILD (SMD = 0.39; 95% CI: 0.17–0.62; P  = 0.0006). In a region-based subgroup analysis, ACPA titer in Asian, European, and African populations was significantly related to the risk of RA-ILD, while there was no significant correlation in the Americans (SMD =  − 0.03; 95% CI: − 0.89–0.83; P = 0.95), especially in the USA (SMD = 0.37; 95% CI: − 0.26–0.99; P = 0.25). In addition, serum positive RF increased the risk of RA-ILD (OR = 2.85; 95% CI: 2.19–3.71; P