Transforming growth factor-beta is increased in sputum from individuals with rheumatoid arthritis-associated pulmonary fibrosis

BACKGROUND: Interstitial lung disease (ILD) develops in 5-10% of patients with RA and contributes significantly to morbidity and mortality, particularly in those with a fibrotic phenotype. Yet, biomarkers to reliably identify RA patients with underlying pulmonary fibrosis are inadequate. Herein, we used sputum to identify lung-based biomarkers that distinguish RA patients with underlying pulmonary fibrosis and may better inform underlying pathogenesis in RA-ILD. METHODS: We included 37 RA patients with pulmonary fibrosis (RA-PF) and 30 RA patients without ILD (RA-no-ILD). Induced sputum and serum were tested for TGF-β levels by immunoassay. DNA was extracted to determine presence of the MUC5B ILD-risk allele ('T'). High-resolution CT (HRCT) and pulmonary function tests (PFTs) were completed within 3 months of sputum collection and quantified to determine lung disease severity. RESULTS: Sputum TGF-β was significantly elevated in individuals with RA-PF compared with RA-no-ILD (P < 0.001) and correlated with more fibrosis on HRCT (P = 0.005) and lower forced vital capacity (P = 0.006) and diffusion capacity of carbon monoxide (P = 0.044) on PFTs. Within RA-PF patients, sputum TGF-β was higher in those with the MUC5B ILD-risk genotype (GT/TT) (P = 0.038). There were no differences in serum levels of TGF-β between groups. CONCLUSION: We demonstrate that sputum levels of TGF-β are significantly elevated in individuals with RA-PF, correlate with lung disease severity, and are elevated in those with the MUC5B ILD-risk polymorphism. These findings could identify novel approaches to ILD screening in RA and potential targeted therapeutic strategies for RA-ILD.