Anti-cyclic citrullinated Peptide antibody is associated with interstitial lung disease in patients with rheumatoid arthritis

PLoS One. 2014 Apr 17;9(4):e92449. doi: 10.1371/journal.pone.0092449. eCollection 2014.


Objective: Patients with rheumatoid arthritis (RA) are at risk to develop RA-associated interstitial lung disease (RA-ILD). This retrospective study aimed to investigate the potential association of the positivity of serum anti-cyclic citrullinated peptide antibody (anti-CCP2) and rheumatoid factor (RF) with RA-ILD in RA patients.

Methods: A total of 285 RA patients were recruited at the inpatient service of Peking Union Medical College Hospital in China between 2004 and 2013. Individual patients were evaluated for the evidence of ILD. The concentrations of serum anti-CCP2 and RF in individual patients were measured. The potential risk factors for ILD in RA patients were assessed by univariate and multivariate models.

Results: There were 71 RA patients with RA-ILD, accounting for 24.9% in this population. The positive rates of anti-CCP2 and RF in the patients with RA-ILD were significantly higher than that in the patients with RA-only (88.7% vs. 67.3%, p<0.001; 84.5% vs. 70.6%, p = 0.02, respectively). Univariate and multivariate logistic regression analysis revealed that RA patients with positive serum anti-CCP2, but not RF, were associated with an increased risk of ILD (crude odds ratio [cOR] 3.83, 95% confidence interval [CI] 1.74-8.43, p<0.001; adjusted odds ratio [aOR] 3.50, 95% CI 1.52-8.04, p<0.001).

Conclusion: Our findings suggest that positive serum anti-CCP2, but not RF, may be associated with RA-ILD in RA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / complications*
  • Arthritis, Rheumatoid / diagnostic imaging
  • Autoantibodies / blood*
  • Autoantibodies / immunology*
  • Female
  • Humans
  • Lung Diseases, Interstitial / complications*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptides, Cyclic / immunology*
  • Retrospective Studies
  • Rheumatoid Factor / blood
  • Tomography, X-Ray Computed


  • Autoantibodies
  • Peptides, Cyclic
  • cyclic citrullinated peptide
  • Rheumatoid Factor

Grant support

This study is supported by the grants of the National Natural Science Foundation of China (30972731, 81172859, 81273312, 81302594), the National High Technology Research and Development Project of China (2011AA020111, 2012AA02A513), the National Major Scientific and Technological Special Project (2012ZX09303006-002), the Research Special Fund for Public Welfare Industry of Health (201202004), the Capital Health Research and Development of Special (2011-4001-02), and the National laboratory Special Fund (2060204). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.