Brief Report: Airways abnormalities and rheumatoid arthritis–related autoantibodies in subjects without arthritis: Early injury or initiating site of autoimmunity?

Abstract

Objective To evaluate the presence of pulmonary abnormalities in subjects with rheumatoid arthritis (RA)-related autoantibody (Ab) positivity without inflammatory arthritis (IA). Methods 42 subjects without IA but with elevations of anti-cyclic citrullinated peptide antibodies and/or 2 or more rheumatoid factor isotypes (a profile that is 96% specific for RA), 15 Ab(−) controls and 12 patients with early established seropositive RA (<1 year duration) underwent spirometry and high-resolution computed tomographic (HRCT) lung imaging. Results The median age of Ab(+) subjects was 54 years-old, 52% were female and 38% were smokers (not significantly different than Ab(−) controls). No Ab(+) subject had IA on joint examination. On HRCT, 76% of Ab(+) subjects had airways abnormalities including bronchial wall thickening, bronchiectasis, centrilobular opacities and air trapping, compared to 33% of Ab(−) controls (p=0.005). The Ab(+) subjects had similar prevalence and type of lung abnormalities compared to patients with early RA. Two Ab(+) subjects with airways disease developed IA classifiable as articular RA ~13 months after lung evaluation. Conclusion Airways abnormalities that are consistent with inflammation are common in Ab(+) subjects without IA, and similar to airways abnormalities seen in early RA. These findings suggest that the lung may be an early site of autoimmune-related injury, and potentially a site of generation of RA-related autoimmunity. Further studies are needed to define the mechanistic role of lung inflammation in the development of RA.

Identification of Citrullinated Hsp90 Isoforms as Novel Autoantigens in Rheumatoid Arthritis–Associated Interstitial Lung Disease

“…Although patients possessing these autoantibodies manifested greater levels of RF and higher (mean) anti-CCP-2 concentrations in conjunction with a trend toward shared epitope positivity, other parameters of articular and global disease activity did not differ significantly between these subgroups. Collectively, however, these data not only provided initial validation of our "reverse immunophenotyping" approach as a viable tool in biomarker discovery, but also supported an emerging paradigm featuring the lung as an important site of protein citrullination and immune-mediated injury in RA (19,28,29).…”

Increased disease activity, severity and autoantibody positivity in rheumatoid arthritis patients with co‐existent bronchiectasis

“…Recently, Demoruelle and co-workers 16 have identified an association between anti-CCP positive subjects without inflammatory arthritis and the presence of airway abnormalities on HRCT. This evidence supports the hypothesis that the lung may be an initiating site for the development of RA.…”

Review: Preclinical Rheumatoid Arthritis: Progress Toward Prevention

“…Structural and immunologic abnormalities have also been reported in the lungs of individuals at-risk for RA (28)(29)(30). At-risk individuals without arthritis who were seropositive for ACPAs were found to have a similar prevalence of airway abnormalities on HRCT when compared to matched RA patients (28), and rheumatoid-type lung disease was found in seropositive individuals who later progressed to develop RA (30).…”

“…In patients with new-onset RA, PD status rather than RA per se influences oral microbial diversity. Harvey et al (24) Anti-CCP antibodies (28) Airways disease on HRCT imaging Seropositive individuals without arthritis had higher prevalence of airways disease on HRCT imaging compared to seronegative matched controls. Willis et al (29) Sputum autoantibodies (ACPAs and RF) 39% of seronegative at-risk individuals were positive for $1 RA-related autoantibody in the sputum; at-risk seropositive subjects had similar prevalence of RA-related autoantibodies in the sputum and serum; patients with early RA had higher autoantibody prevalence in the serum than in the sputum.…”