AUTHOR=Pulito-Cueto Verónica , Remuzgo-Martínez Sara , Genre Fernanda , Atienza-Mateo Belén , Mora-Cuesta Víctor M. , Iturbe-Fernández David , Lera-Gómez Leticia , Sebastián Mora-Gil María , Prieto-Peña Diana , Portilla Virginia , Blanco Ricardo , Corrales Alfonso , Ocejo-Vinyals J. Gonzalo , Gualillo Oreste , Ferraz-Amaro Iván , Cifrián José M. , López-Mejías Raquel , González-Gay Miguel A. TITLE=Elevated VCAM-1, MCP-1 and ADMA serum levels related to pulmonary fibrosis of interstitial lung disease associated with rheumatoid arthritis JOURNAL=Frontiers in Molecular Biosciences VOLUME=9 YEAR=2022 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.1056121 DOI=10.3389/fmolb.2022.1056121 ISSN=2296-889X 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+.