Fragmented gelsolins are increased in rheumatoid arthritis-associated interstitial lung disease with usual interstitial pneumonia pattern

Abstract

Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) occurs in 10%–30% of patients with RA, and interstitial lung disease (ILD) is associated with increased mortality in up to 10% of patients with RA. The pathogenesis of RA-ILD is virtually unknown. The aim of this study is to investigate the proteins related to UIP pattern by comparing to OP pattern in RA-ILD using proteome analysis of bronchoalveolar lavage fluid (BALF). Methods: Proteomic differences in BALF were compared between the UIP pattern and OP pattern by examining BALF from 5 patients with the UIP pattern and 7 patients with the OP pattern by two-dimensional gel electrophoresis and mass spectrometry. Results: In individual comparisons of BALF samples, the levels of the protein gelsolin and Ig kappa chain C region were significantly higher in the UIP pattern than in the OP pattern. In contrast, the levels of α-1 antitrypsin, CRP, haptoglobin β, and surfactant protein A (isoform number 5) were all significantly higher in the OP pattern than in the UIP pattern. Gelsolin was cleaved into two fragments, a C-terminal half and N-terminal half, and the levels of both were significantly higher in the UIP pattern than in the OP pattern. Conclusions: Fragmented gelsolins may be associated with the pathogenesis of fibrosis in RA-ILD.

Keywords

• Bronchoalveolar lavage fluid
• Gelsolin
• Interstitial pneumonia
• Proteomics
• Rheumatoid arthritis