Plasma-derived exosomal miRNAs as non-invasive biomarkers for lung involvement in systemic sclerosis

Abstract

<b>Background:</b> Systemic sclerosis (SSc) is a chronic autoimmune disease with an unknown etiology, associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. It is crucial to identify early biomarkers of lung involvement to prevent its damage and the progression of SSc-ILD. <b>Objective:</b> The aim of this study was to determine if plasma exosomal microRNAs (miRNAs) may be good markers to identify SSc-ILD patients. <b>Methods:</b> We conducted a genome-wide analysis of miRNAs in plasma-derived exosomes from SSc patients with ILD (SSc-ILD, n=10), without ILD (SSc-no ILD, n=10) and healthy subjects (HS, n=10), and investigated differentially expressed miRNAs between SSc-ILD and SSc-no ILD patients. <b>Results:</b> We identified a subset of 17 altered exosomal miRNAs associated to lung impairment, 7 upregulated and 10 downregulated in SSc-ILD (FDR&lt;0.1) (Figure 1). Functional analysis demonstrated that these miRNAs are associated to several pathophysiological processes involved in ILD, highlighting the potential interest of exosomal miRNAs as promising biomarkers and therapeutic targets of SSc-ILD. Fig. 1: Subset of exosomal miRNAs associated to lung impairment. <b>Conclusions:</b> For the first time, we identified potential biomarkers of lung involvement in SSc patients from plasma-derived exosomes. These candidates should be investigated in large independent cohorts to confirm their biomarker status for SSc-ILD.