Background Interstitial lung disease (ILD) is one of the main causes of death in patients with rheumatoid arthritis (RA), constituting its early diagnosis in these patients a challenge for the clinicians [1]. In this sense, pulmonary endothelial activation is one of the essential steps to the development of lung lesions [2,3]. In this regard, endothelin-1 (ET-1), the most potent endogenous vasoconstrictor, has been described as a profibrotic molecule [3]. Accordingly, it is plausible to think that ET-1 is involved in the pathophysiology of RA-ILD⁺.

Objectives To explore the role of ET-1 as a biomarker of pulmonary fibrosis in RA-ILD⁺.

Methods Peripheral venous blood was collected from 21 RA-ILD⁺ patients and two comparative groups: 25 RA-ILD^- patients and 21 idiopathic pulmonary fibrosis (IPF) patients. All the subjects were recruited from the Rheumatology and Pneumology departments of Hospital Universitario Marqués de Valdecilla, Santander, Spain. Serum levels of ET-1 were determined by ELISA.

Results RA-ILD⁺ patients showed increased levels of ET-1 compared to those with RA-ILD^- (p<0.01, Figure 1A). Interestingly, the ability of serum ET-1 levels to discriminate patients with RA-ILD⁺ from those with RA-ILD^- was further confirmed by receiver operating characteristic curves (area under the curve: 0.77, p<0.01, Figure 1B). The optimal cutoff value for ET-1 showing the best sensitivity and specificity was 1.02 pg/mL. Moreover, patients with RA-ILD⁺ presented similar levels of ET-1 than those with IPF (p=0.50, Figure 1A). Additionally, a negative correlation between ET-1 serum levels and both forced vital capacity and forced expiratory volumen at first second was disclosed in patients with RA-ILD⁺ (r=-0.56, p=0.04 and r=-0.65, p=0.01, respectively).

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Figure 1.

ET-1 for the diagnosis of RA-ILD⁺. Differences in serum levels of ET-1 between patients with RA-ILD⁺ and those with RA-ILD^- and IPF (A), as well as ROC curves analysis of ET-1 for the discrimination of RA-ILD⁺ from RA-ILD^- (B). ET-1: endothelin 1; RA: rheumatoid arthritis; ILD: interstitial lung disease; IPF: idiopathic pulmonary fibrosis;. Significant results are highlighted in bold.

Conclusion Our study suggests that ET-1 levels are linked to lung injury and worse lung function, supporting its role as a potential blood biomarker of ILD in RA patients.

References [1]Expert Rev Clin Immunol. 2021;17(5):485-497;

[2]JCI Insight. 2021;6(22):e125635;

[3]Am J Respir Cell Mol Biol. 2010;42(1):16-20.

Acknowledgements VP-C is supported by funds of PI18/00042 from Instituto de Salud Carlos III (ISCIII), co-funded by European Regional Development Fund; MSM-G is financed by funds of TRANS-VAL 22/01 from IDIVAL; RL-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).

Disclosure of Interests Verónica Pulito-Cueto: None declared, Sara Remuzgo Martinez: None declared, Belén Atienza-Mateo: None declared, Fernanda Genre Romero: None declared, Victor Manuel Mora-Cuesta: None declared, David Iturbe Fernández: None declared, María Sebastián Mora-Gil: None declared, Virginia Portilla: None declared, Alfonso Corrales: None declared, Iván Ferraz-Amaro: None declared, Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Consultant of: Abbvie, Pfizer, Roche, Bristol-Myers, Janssen and MSD, Grant/research support from: Abbvie, MSD and Roche, Jose Manuel Cifrián-Martínez: None declared, Raquel López-Mejías: None declared, Miguel A González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi, Lilly, Celgene, MSD and GSK, Grant/research support from: Abbvie, MSD, Jansen and Roche.