Elevated VCAM-1, MCP-1 and ADMA serum levels related to pulmonary fibrosis of interstitial lung disease associated with rheumatoid arthritis
Verónica Pulito‐Cueto, Sara Remuzgo‐Martínez, Fernanda Genre, Belén Atienza‐Mateo, Víctor Manuel Mora Cuesta, David Iturbe‐Fernández, Leticia Lera‐Gómez, M. Sebastián Mora-Gil, D. Prieto-Peña, Virginia Portilla, Ricardo Blanco, Alfonso Corrales, J. Gonzalo Ocejo‐Vinyals, Oreste Gualillo, Iván Ferraz‐Amaro, José M. Cifrián, Raquel López‐Mejías, Miguel Á. González‐Gay
Abstract
Introduction: Early diagnosis of interstitial lung disease (ILD) associated with rheumatoid arthritis (RA) constitutes a challenge for the clinicians. Pulmonary vasculopathy is relevant in the development of interstitial lung disease. Accordingly, we aimed to explore the role of vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and asymmetric dimethylarginine (ADMA), key molecules in the vasculopathy, as potential biomarkers of pulmonary fibrosis in RA-ILD + . Methods: We included 21 RA-ILD + patients and two comparative groups: 25 RA-ILD - patients and 21 idiopathic pulmonary fibrosis (IPF) patients. Serum levels of the molecules were determined by ELISA, and mRNA expression was quantified by qPCR. Results: VCAM-1, MCP-1 and ADMA serum levels were increased in RA-ILD + patients in relation to RA-ILD - and IPF patients. Additionally, RA-ILD + patients exhibited increased CCL2 (gene encoding MCP-1) and decreased PRMT1 (gene related to ADMA synthesis) mRNA expression in relation to RA-ILD - patients. A lower expression of VCAM1 , CCL2 , and PRMT1 was observed in RA-ILD + patients when compared with those with IPF. Furthermore, MCP-1 serum levels and PRMT1 mRNA expression were positively correlated with RA duration, and ADMA serum levels were positively associated with C-reactive protein in RA-ILD + patients. Conclusion: Our study suggests that VCAM-1, MCP-1 and ADMA could be considered as useful biomarkers to identify ILD in RA patients, as well as to discriminate RA-ILD + from IPF, contributing to the early diagnosis of RA-ILD + .