WASHINGTON – Specific anticitrullinated peptide antibody levels were significantly higher in rheumatoid arthritis patients with interstitial lung disease than in those without lung disease, based on data from 177 patients.
Complications and death are common in rheumatoid arthritis (RA) patients with interstitial lung disease (ILD), and the findings "may implicate the lung as a site in which protein citrullination initiates epitope spreading and propagation of RA," said Dr. Jon T. Giles of Columbia University in New York.
Jon T. Giles
To determine the association of anticitrullinated peptide antibodies (ACPA) with ILD, Dr. Giles and his colleagues reviewed data from multidetector computed tomography images and concurrent serum samples for 177 RA patients. The mean age of the patients was 59 years, 60% were women, and 11% were smokers.
A total of 57 patients (32%) showed some evidence of ILD on imaging, and 32 (18%) had ILD scores of 3 U or higher, Dr. Giles said at the meeting. Overall, levels of anticyclic citrullinated peptide (anti-CCP) and 17 specific ACPAs ranged from 46% to 273% higher in patients with ILD than in those without ILD. Patients with ILD were more likely to be male, to smoke, and to have a history of prednisone and leflunomide use as well as rheumatoid factor and anti-CCP seropositivity compared with patients without ILD, said Dr. Giles.
Anti-CCP seropositivity was significantly more common among patients with any ILD vs. those without ILD (89% vs. 69%), and the seropositivity was even more common (94%) in patients with ILD scores of 3 U or higher.
Higher levels of seven or more ACPAs were significantly more common in patients with reticulation, honeycombing, or traction bronchiectasis than in those with no ILD (40% vs. 18%).
In addition, higher levels of seven or more ACPAs were significantly more common in patients with evidence of restriction on a pulmonary function test and/or decreased results on a diffusing capacity of the lungs for carbon monoxide test compared with those without ILD (39% vs. 20%). The differences were significant after adjustment for age, sex, smoking status, disease activity score (using DAS28), and current prednisone and leflunomide use.
Levels of antibodies targeting noncitrullinated proteins were not significantly higher in patients with ILD, which "suggests a specificity for ACPA in the association," Dr. Giles said.
"Another mechanistic possibility is that ACPA[s] targeting citrullinated synovial antigens are generated and mediate remote pathogenic effects upon circulating to the lungs, where their cognate citrullinated proteins may also be present," he said.
The findings were limited in part by the use of multidetector computed tomography, which differs in slice thickness from high-resolution CT, Dr. Giles noted. But the strengths of the research include the multiple measures of pulmonary disease, he said.
Dr. Giles said he had no financial conflicts to disclose. The study was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American College of Rheumatology’s Within Our Reach Campaign.