Endothelin-1 as a biomarker of idiopathic pulmonary fibrosis and interstitial lung disease associated with autoimmune diseases

The aim of this study was to determine the role of endothelin-1 (ET-1), a molecule involved in multiple vascular and fibrosing abnormalities, as a biomarker of interstitial lung disease (ILD), as well as its use for the differential diagnosis between idiopathic pulmonary fibrosis (IPF) and ILD associated with autoimmune diseases (AD-ILD), using a large and well-defined cohort of patients with ILD. A total of 112 patients with IPF, 91 patients with AD-ILD (28 rheumatoid arthritis (RA), 26 systemic sclerosis, 20 idiopathic inflammatory myositis and 17 interstitial pneumonia with autoimmune features) and 44 healthy controls were included. ET-1 serum levels were determined by enzyme-linked immunosorbent assay. A significant increase in ET-1 levels was found in patients with IPF compared to controls. Likewise, AD-ILD patients also showed higher ET-1 levels than controls when the whole cohort was stratified by the type of AD. Similar ET-1 levels were found in IPF and AD-ILD patients, regardless of the underlying AD. Interestingly, increased ET-1 levels were correlated with worse lung function in IPF and RA-ILD patients. Our study supports that serum ET-1 may be useful as a biomarker of ILD, although it could not help in the differential diagnosis between IPF and AD-ILD. Moreover, ET-1 levels may be associated with ILD severity.Funding: This study was supported by FUAM 20/32 (Cátedra UAM-Roche EPID Futuro) and partially supported by a grant from the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR 474- 2017). V.P.-C. is supported by funds of PI18/00042 from the Instituto de Salud Carlos III (ISCIII), co-funded by European Regional Development Fund (ERDF); F.G. is supported by funds of the RICORS Program (RD21/0002/0025) from ISCIII, co-funded by the European Union; R.L.-M. is a recipient of a Miguel Servet type II Program fellowship from ISCIII, co-funded by the European Social Fund, ‘Investing in your future´ (CPII21/00004); O.G. is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and ERDF [RD16/0012/0014 (RIER)]; S.R.-M. was supported by funds of the RETICS Program (RD16/0012/0009) from ISCIII, co-funded by ERDF. Acknowledgments: We wish to thank all the subjects for their essential collaboration in this study