Endothelial Progenitor Cells as a Potential Biomarker in Interstitial Lung Disease Associated with Rheumatoid Arthritis.

Verónica Pulito-Cueto,José M Cifrián,Miguel A González-Gay,Diana Prieto-Peña,Virginia Portilla,David Iturbe-Fernández,Ricardo Blanco,Alfonso Corrales,Sonia Fernández-Rozas,Belén Atienza-Mateo,Javier Rodríguez-Carrio,Fernanda Genre,Sara Remuzgo-Martínez,Pilar Alonso-Lecue,Víctor M Mora-Cuesta,Raquel López-Mejías,Oreste Gualillo,Leticia Lera-Gómez

doi:10.3390/jcm9124098

Abstract

Interstitial lung disease (ILD) increases morbidity and mortality in patients with rheumatoid arthritis (RA). Although the pathogenesis of ILD associated with RA (RA-ILD+) remains poorly defined, vascular tissue is crucial in lung physiology. In this context, endothelial progenitor cells (EPC) are involved in endothelial tissue repair. However, little is known about their implication in RA-ILD+. Accordingly, we aimed to investigate the potential role of EPC related to endothelial damage in RA-ILD+. EPC quantification in peripheral blood from 80 individuals (20 RA-ILD+ patients, 25 RA-ILD− patients, 21 idiopathic pulmonary fibrosis (IPF) patients, and 14 healthy controls) was performed by flow cytometry. EPC were considered as CD34+, CD45low, CD309+ and CD133+. A significant increase in EPC frequency in RA-ILD+ patients, as well as in RA-ILD− and IPF patients, was found when compared with controls (p < 0.001, p = 0.02 and p < 0.001, respectively). RA-ILD+ patients exhibited a higher EPC frequency than the RA-ILD− ones (p = 0.003), but lower than IPF patients (p < 0.001). Our results suggest that EPC increase may represent a reparative compensatory mechanism in patients with RA-ILD+. The degree of EPC frequency may help to identify the presence of ILD in RA patients and to discriminate RA-ILD+ from IPF.

Highlights

Interstitial lung disease (ILD) is one of the most feared complications in patients with rheumatoid arthritis (RA), increasing their morbidity and mortality [1,2]
Statistically significant differences were found between patients with RA-ILD- and RA-ILD+ regarding the following clinical features: rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACPA) status, C-reactive protein (CRP) levels, forced expiratory volume in one second /forced vital capacity (FEV1/FVC) (% predicted), diffusing capacity of the lung for carbon monoxide (DLCO) (% predicted), and therapies received (Table 1)
The purpose of this work was to determine the potential role of endothelial progenitor cells (EPC) in the pathogenesis related to endothelial damage in RA-ILD+

Summary

Introduction

Interstitial lung disease (ILD) is one of the most feared complications in patients with rheumatoid arthritis (RA), increasing their morbidity and mortality [1,2]. Some patients initially defined as having IPF may be diagnosed with RA-ILD+ [4] Based on these data, a better understanding of the pathogenesis of RA-ILD+ is crucial. Vascular tissue plays a key role in lung homeostasis, contributing both to physiological and pathological processes [5]. In this context, the maintenance of the endothelium through its repair and regeneration is guaranteed by a population of cells described by Asahara et al and termed as endothelial progenitor cells (EPC) [6]. Given that EPC have been suggested as a marker of endothelial damage in several diseases, the understanding of the role of EPC in RA-ILD+ may be critical for a better knowledge of the vascular pathophysiology that characterizes this disease

Objectives

Methods

Results

Conclusion