Document Type
Article
Publication Date
12-18-2024
Abstract
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.
Recommended Citation
Wilson, Timothy M.; Bolt, Matthew; Stahly, Andrew; Lee, Joyce S.; Bang, Tami J.; Sachs, Peter B.; Deane, Kevin D.; Humphries, Stephen M.; Solomon, Joshua J.; and Demoruelle, M. Kristen, "Transforming Growth Factor-Beta Is Increased in Sputum From Individuals With Rheumatoid Arthritis-Associated Pulmonary Fibrosis" (2024). Division of Rheumatology Faculty Papers. Paper 2.
https://jdc.jefferson.edu/rheumatologyfp/2
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
Language
English
Comments
This is the author's final published version in Rheumatology, Volume 64, Issue 6, June 2025, Pages 3989 - 3995.
The published version is available at https://doi.org/10.1093/rheumatology/keae697. Copyright © The Author(s).