Structural changes and antibody enrichment in the lungs are early features of anti-citrullinated protein antibody-positive rheumatoid arthritis

Arthritis Rheumatol. 2014 Jan;66(1):31-9. doi: 10.1002/art.38201.


Objective: It has been suggested that immunologic events in the lungs may be involved in triggering immunity, in particular production of anti-citrullinated protein antibodies (ACPAs) during early phases of rheumatoid arthritis (RA). The aim of this study was to investigate the structural and immunologic features of the lungs in incident cases of early RA in relation to ACPA presence and smoking status.

Methods: High-resolution computed tomography (HRCT) was used to examine the lungs of 105 patients with early, untreated RA (70 with ACPA-positive RA and 35 with ACPA-negative RA) and 43 healthy individuals. Bronchoscopy with collection of bronchoalveolar lavage (BAL) fluid and mucosal bronchial biopsy specimens was performed in 23 RA patients. The presence of citrullinated proteins in the bronchial tissue was detected by immunohistochemical staining. ACPAs (detected with an anti-cyclic citrullinated peptide 2 test) and total Ig levels were determined in the sera and BAL fluid of RA patients.

Results: HRCT imaging revealed that 63% of ACPA-positive RA patients had parenchymal lung abnormalities, compared with only 37% of ACPA-negative RA patients and 30% of healthy controls (each P < 0.05). These significant differences remained after adjustment for smoking status. Airway changes detected by HRCT were more frequent in RA patients than in healthy controls (66% versus 42%; P < 0.05), but there was no difference between ACPA-positive and ACPA-negative RA patients. Immunohistochemical studies of the bronchial tissue showed increased staining for citrullinated proteins in ACPA-positive RA patients compared with ACPA-negative RA patients (P < 0.05). ACPA levels were relatively higher in the BAL fluid as compared with the sera of ACPA-positive RA patients, suggesting that there is local production of ACPAs in the lungs of these patients.

Conclusion: The presence of ACPAs is associated with parenchymal lung abnormalities, site-specific citrullination, and antibody enrichment in the lungs early in the development of ACPA-positive RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Arthritis, Rheumatoid / diagnostic imaging
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Autoantibodies / immunology*
  • Bronchoalveolar Lavage
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology*
  • Bronchoscopy
  • Case-Control Studies
  • Female
  • Humans
  • Immunoglobulins / immunology
  • Lung / diagnostic imaging
  • Lung / immunology*
  • Lung / pathology
  • Male
  • Middle Aged
  • Peptides, Cyclic / immunology*
  • Spirometry
  • Tomography, X-Ray Computed
  • Young Adult


  • Autoantibodies
  • Immunoglobulins
  • Peptides, Cyclic
  • cyclic citrullinated peptide