E-Selectin, ICAM-1, and ET-1 Biomarkers Address the Concern of the Challenging Diagnosis of Interstitial Lung Disease in Patients with Autoimmune Diseases

Int J Mol Sci. 2023 Aug 7;24(15):12518. doi: 10.3390/ijms241512518.

Abstract

Interstitial lung disease (ILD) constitutes the most critical comorbidity in autoimmune diseases (ADs) and its early diagnosis remains a challenge for clinicians. Accordingly, we evaluated whether E-selectin, ICAM-1, and ET-1, key molecules in endothelial damage, could be useful biomarkers for the detection of AD-ILD+. We recruited patients with rheumatoid arthritis (RA)-ILD+ (n = 21) and systemic sclerosis (SSc)-ILD+ (n = 21). We included comparison groups of patients: RA-ILD- (n = 25), SSc-ILD- (n = 20), and idiopathic pulmonary fibrosis (IPF) (n = 21). Serum levels of these proteins were determined by ELISA. E-selectin, ICAM-1, and ET-1 serum levels were increased in RA-ILD+ and IPF patients in comparison to RA-ILD- patients. Additionally, SSc-ILD+ and IPF patients exhibited higher ICAM-1 levels than those with SSc-ILD-. The ability of E-selectin, ICAM-1, and ET-1 to discriminate RA-ILD+ from RA-ILD- patients, and ICAM-1 to distinguish SSc-ILD+ from SSc-ILD- patients was confirmed using ROC curve analysis. Furthermore, elevated levels of ET-1 and E-selectin correlated with lung function decline in RA-ILD+ and SSc-ILD+ patients, respectively. In conclusion, our findings support the relevant role of E-selectin, ICAM-1, and ET-1 in RA-ILD+ patients as well as of ICAM-1 in SSc-ILD+ patients, constituting potential screening blood biomarkers of ILD in AD. Moreover, this study suggests ET-1 and E-selectin as possible indicators of worsening lung function in RA-ILD+ and SSc-ILD+ patients, respectively.

Keywords: E-selectin; ET-1; ICAM-1; autoimmune diseases; biomarkers; interstitial lung disease; pulmonary fibrosis; rheumatoid arthritis; systemic sclerosis.

MeSH terms

  • Arthritis, Rheumatoid* / complications
  • Arthritis, Rheumatoid* / diagnosis
  • Autoimmune Diseases* / complications
  • Autoimmune Diseases* / diagnosis
  • Biomarkers
  • E-Selectin
  • Humans
  • Idiopathic Pulmonary Fibrosis* / complications
  • Idiopathic Pulmonary Fibrosis* / diagnosis
  • Intercellular Adhesion Molecule-1
  • Lung
  • Lung Diseases, Interstitial* / complications
  • Lung Diseases, Interstitial* / diagnosis
  • Scleroderma, Systemic* / complications
  • Scleroderma, Systemic* / diagnosis

Substances

  • Intercellular Adhesion Molecule-1
  • E-Selectin
  • Biomarkers