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

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). 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. 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. Fragmented gelsolins may be associated with the pathogenesis of fibrosis in RA-ILD.

Suhara K ，Miyazaki Y ，Okamoto T ，Ishizuka M ，Tsuchiya K ，Inase N ... -  《-》

Proteome analysis of bronchoalveolar lavage fluid in chronic hypersensitivity pneumonitis.

Okamoto T ，Miyazaki Y ，Shirahama R ，Tamaoka M ，Inase N ... -  《-》

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung.

In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-usual interstitial pneumonia (RA-UIP).NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1β and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1β and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1β were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1β and partly IL-18 secretion, in contrast to controls, which showed robust IL-1β and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1β, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1β levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1β suggesting the NLRP3 pathway could be further activated.Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis.

Lasithiotaki I ，Giannarakis I ，Tsitoura E ，Samara KD ，Margaritopoulos GA ，Choulaki C ，Vasarmidi E ，Tzanakis N ，Voloudaki A ，Sidiropoulos P ，Siafakas NM ，Antoniou KM ... -  《-》

Histopathologic pattern and clinical features of rheumatoid arthritis-associated interstitial lung disease.

Lee HK ，Kim DS ，Yoo B ，Seo JB ，Rho JY ，Colby TV ，Kitaichi M ... -  《CHEST》

Related factors, increased mortality and causes of death in patients with rheumatoid arthritis-associated interstitial lung disease.

Kakutani T ，Hashimoto A ，Tominaga A ，Kodama K ，Nogi S ，Tsuno H ，Ogihara H ，Nunokawa T ，Komiya A ，Furukawa H ，Tohma S ，Matsui T ... -  《-》