Uncovering mirnomes of patients with interstitial lung diseases and an underlying autoimmune process

Interstitial lung disease (ILD) is a major manifestation of systemic autoimmune rheumatic diseases (SARD). Unmet needs in this population are the early identification of patients at risk of functional deterioration and tailoring therapies on a pathophysiological basis. The study of microRNA is being applied to trace pathogenetic mechanisms and as predictive tool in complex diseases. We have performed bulk small-RNA sequencing in sera from 24 patients with SARD-associated ILD and 5 healthy subjects, in order to identify differentially expressed molecules in the patients and in disease subgroups. Variables of the study included disease duration, radiographic patterns, clinical diagnosis, alterations in nailfold capillaroscopy, functional status, levels of Krebs von den Lungen 6 (KL-6), presence of rheumatoid factor, and outcomes over the following 18-month period. The patients showed 13 differentially expressed miRNA, out of which Let-7i-5p associated with higher KL-6 levels, whereas miR-151a-5p was increased during early disase and miR-483-5p was higher in patients with microvascular involvement. The latter subgroup displayed a specific signature, characterized by the up-regulation of the miR-320 and miR-10 families. Also to underscore was the value of miR-223, miR-142-5p, miR-145-5p, miR-23a-5p, miR-29a-3p, miR-320c, miR-320d and miR-10a-3p in forecasting a progressive phenotype. Functional analysis pointed to an up-regulation of profibrotic miRNA as early biomarkers of poor outcome. On the whole, our data uncover for the first time miRNomes associated to SARD-ILD in an exporatory approach. Whether or not the miRNA shown up in this study applies to the whole population of SARD-ILD warrants confirmation in further research.