Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease

Abstract

Summary Objective We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD). Methods The study sample included 74 subjects with respiratory symptoms, evaluated January 2008–January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation. Results The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity (n=33), three developed the articular manifestations of RA during a median follow-up of 449 days. Conclusion We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation.

Rheumatoid arthritis-associated lung disease

“…Anti-CCP antibodies have also been associated with the development of airway disease [2]. There is growing evidence that rheumatoid arthritis begins in the lungs, a theory supported by a subgroup of patients who are anti-CCP positive with lung disease but have no articular manifestations [22,23]. Additionally, a form of reactive lymphoid tissue known as inducible bronchus-associated lymphoid tissue (BALT) has been found in patients with rheumatoid arthritis-related lung disease and is associated with local production of inflammatory cytokines and anti-CCP antibodies [24].…”

Significance of connective tissue diseases features in pulmonary fibrosis

“…Reproduced from [6] In a similar approach, several studies have evaluated the potential relevance of evaluating organ-specific manifestations of CTD. In a group of 74 patients with respiratory symptoms and the presence of anti-cyclic citrullinated peptide antibodies (the majority of whom with isolated airways disease, some with isolated ILD or mixed airways disease and ILD including the syndrome of combined pulmonary fibrosis and emphysema), three developed articular manifestations of rheumatoid arthritis during a median follow-up of 449 days [42]. In patients with ILD who were apparently idiopathic (and with no definable CTD), occult Sjögren's syndrome was detected by systematic salivary gland biopsy in 34% of cases, including 62% with presence of anti-SSa antibodies and 77% with sicca symptoms [43].…”

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).…”