0123: Increase of Serum Endothelin-1 Levels in Patients with Interstitial Lung Disease Associated with Autoimmune Diseases

Sara Remuzgo-Martinez¹, Belén Atienza-Mateo¹, Veronica Pulito-Cueto¹, Fernanda Genre¹, Víctor M. Mora-Cuesta¹, David Iturbe-Fernández¹, Virgi Portilla¹, María Sebastián Mora-Gil¹, J Gonzalo Ocejo-Vinyals², Oreste Gualillo³, Alfonso Corrales¹, Santos Castañeda⁴, Raquel Lopez Mejias⁵, José M. Cifrián¹ and Miguel Ángel González-Gay⁶, ¹Research Group on Genetic Epidemiology and Atherosclerosis in Systemic Diseases and in Metabolic Bone Diseases of the Musculoskeletal System, IDIVAL; and Department of Rheumatology, Hospital Universitario Marqués de Valdecilla, Santander, Spain, ²Department of Immunology, Hospital Universitario Marqués de Valdecilla, Santander, Spain, ³Hospital Clínico Universitario de Santiago, SERGAS (Servizo Galego de Saude) and IDIS (Instituto de Investigación Sanitaria de Santiago), NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Research Laboratory 9, Santiago de Compostela, Spain, ⁴Division of Rheumatology, Hospital Universitario de La Princesa, IIS-Princesa, Madrid, Spain, ⁵IDIVAL, Santander, Spain, ⁶Department of Medicine and Psychiatry, Universidad de Cantabria; Rheumatology Division, Hospital Universitario Marqués de Valdecilla; Research group on genetic epidemiology and atherosclerosis in systemic diseases and in metabolic diseases of the musculoskeletal system, IDIVAL, Santander, Spain. Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

Background/Purpose: Interstitial lung disease (ILD) may occur in patients with a rheumatic autoimmune disease (AD), increasing their morbidity and mortality [1]. In this regard, the identification of serum biomarkers of AD-ILD is of potential interest. Endothelin-1 (ET-1) is a proinflammatory protein involved in multiple vascular and fibrosing abnormalities [2-3], characteristic processes of AD-ILD. Nevertheless, the role of ET-1 as a biomarker of AD-ILD has not been elucidated yet. Consequently, we determined the role of ET-1 serum levels in a large cohort of patients with ILD associated with different ADs.

Methods:
A total of 104 patients with AD-ILD (28 RA, 26 SSc, 20 idiopathic inflammatory myositis (IIM), 19 interstitial pneumonia with autoimmune features (IPAF), 6 primary SS, 3 SLE and 2 mixed CTD), 115 patients with idiopathic pulmonary fibrosis (IPF) and 49 healthy controls from Hospital Universitario Marqués de Valdecilla (Santander, Spain) were included in this study. ET-1 serum levels were analyzed by enzyme-linked immunosorbent assay.

Results: A significant increase of ET-1 serum levels was found in the whole cohort of patients with AD-ILD compared to healthy controls (mean 1.43 pg/mL versus 0.84 pg/mL, respectively, p< 0.001). In particular, IIM-ILD patients had the highest levels of ET-1, followed by SSc-ILD, mixed CTD, RA-ILD, IPAF, SLE and primary SS patients, who showed the lowest levels of ET-1 (1.78, 1.65, 1.54, 1.43, 1.38, 1.32 and 1.18 pg/mL, respectively). Moreover, similar ET-1 serum levels were found between the whole cohort of patients with AD-ILD and IPF patients (IPF: 1.36 pg/mL). Interestingly, a statistically significant increase of ET-1 serum levels was disclosed when IIM-ILD and SSc-ILD patients were compared to IPF patients (p=0.006 and p=0.030, respectively).

Conclusion: Our study supports that an increase of serum ET-1 levels is characteristic of AD-ILD patients. Furthermore, it suggests that serum ET-1 may be useful as a biomarker for the differential diagnosis between patients with IPF and those with IIM-ILD or SSc-ILD.

References:

1. J Clin Med. 2020 May 26;9(6):1606.
2. Arthritis Rheum. 2003 May;48(5):1190-9.
3. Am J Respir Cell Mol Biol. 2010 Jan;42(1):16-20.

Acknowledgements: Study supported by FUAM20/32 (Cátedra UAM-Roche EPID Futuro) and SEPAR 474-2017. Personal funds: SR-M and VP-C: RD16/0012/0009 (ISCIII-ERDF); FG: RICORS Program RD21/0002/0025 (ISCIII-European Union); RL-M: Miguel Servet type II CPII21/00004 (ISCIII-ESF).


Disclosures: S. Remuzgo-Martinez, None; B. Atienza-Mateo, AbbVie/Abbott, Roche, Pfizer, Celgene, Novartis, Janssen, UCB, Eli Lilly; V. Pulito-Cueto, None; F. Genre, None; V. Mora-Cuesta, None; D. Iturbe-Fernández, None; V. Portilla, None; M. Sebastián Mora-Gil, None; J. Ocejo-Vinyals, None; O. Gualillo, None; A. Corrales, None; S. Castañeda, Roche; R. Lopez Mejias, None; J. Cifrián, None; M. González-Gay, AbbVie/Abbott, Merck/MSD, Janssen, Roche, AbbVie/Abbott, Roche, Sanofi, Eli Lilly, Celgene, Sobi, Merck/MSD.