A Proof-of-Concept Analysis of Plasma-Derived Exosomal microRNAs in Interstitial Pulmonary Fibrosis Secondary to Antisynthetase Syndrome

Abstract

Antisynthetase syndrome (ASSD) is an autoimmune disease characterized by the positivity of autoantibodies against different aminoacyl transfer RNA (tRNA) synthetases. Morbidity and mortality of this disease are highly affected by interstitial lung disease (ILD) which is present in about 80% of patients. In this study, we investigated possible differences in 84 immune-related circulating miRNAs between ASSD patients with and without ILD; we enrolled 15 ASSD patients, 11 with ILD (ILD+) and 4 without ILD (ILD-), and 5 patients with idiopathic pulmonary fibrosis (IPF) as an additional control group. All patients were at disease onset and not on therapy at the time of inclusion. Differentially expressed miRNAs were identified in plasma-derived exosomes, using an miRNA PCR array (MIHS-111ZG, Qiagen, Hilden, Germany); miR-30a-5p and miR-29c-3p were upregulated in ASSD-ILD patients compared to patients without lung involvement (adjusted p-value < 0.05). IPF patients showed higher miR-29c-3p expression levels with respect to both ASSD and ASSD-ILD (p = 0.0005), whereas levels of miR-30a-5p were not different. miR-29c-3p and miR-30a-5p are overexpressed in ASSD-ILD+ patients compared with ILD−. These miRNAs are involved in the regulation of inflammation and fibrosis through their action on NF-κB and TGF-β1. Although the mechanistic role of these miRNAs in ASSD-ILD development has to be elucidated, we suggest that their exosome levels could be useful in identifying patients at risk of ILD.