AB0148 IDENTIFICATION OF CANDIDATE miRNA MOLECULES AS BIOMARKERS IN INTERSTITIAL PNEUMONIA WITH AN UNDERLYING AUTOIMMUNE DISEASE. A DISCOVERY COHORT FROM THE NEREA PROJECT

Background A group of patients with chronic interstitial pneumonia (IP) have an underlying autoimmune disease -typically a connective tissue disorder (CTD)-. In turn, autoimmune-related IP (AIP) processes are highly heterogenous as regards to their clinical presentation, extra-pulmonary features and risk of fibrotic progression. A better understanding of clinically-relevant disease phenotypes is needed in order to tailor therapeutics. Objectives MicroRNA are short non-coding RNAs which orchestrate multiple biological processes by regulating mRNAs via cleavage or translational repression. Circulating levels of miRNA molecules provide excellent information about pathogenic processes in complex diseases, help identify specific disease subgroups and therapeutic targets. Methods We have conducted NGS of small-noncoding RNA in patients with AIP enrolled in the NEREA register of AIP and being followed at any of the Special Multidisciplinary Clinics from the participating Centers. The study population comprised 29 subjects (24 cases, 5 controls; 93% women, 87% newly diagnosed patients). Sixty seven % of the patients were diagnosed with interstitial pneumonia with autoimmune features (IPAF) and all patients had a pulmonary dominant disease at the time of blood sampling. QIAGEN genomic services and a NextSeq (Illumina Inc.) instrument were used. For statistical comparisons, the sample was further segregated according to clinical diagnosis, radiographic pattern, evidence of fibrosis in HRCT, relative levels of Krebs von den Lungen (KL-)6 and type of autoantibodies (classified into those potentially-associated to vasculopathy, the ones typically associated to rheumatoid arthritis, and non-specific ANA). The association was considered true for a p level < 0.02 and a low false discovery rate (FDR), p < 0.1. DIANA tools including the Tarbase v8.0 were used to assess functional pathways with GO and KEGG analysis. Results As compared to the healthy controls, patients with IP showed higher levels of let-7i-5p (1.9-fold, p <0.01), miR-483-5p (3.5-fold, p <0.0005) and the miR-320 family. Fibrotic disease was associated to an up-regulation of the let-7 cluster, miR-151a-5p (2.04-fold, p < 0.01), miR-185-5p (2.4-fold, p 0.011), miR-320a-3p (2-fold, p 0.016), miR-320e (2-fold, p 0.016) and miR-423-5p (1.9-fold, p < 0.01). Besides, there was an up-regulation of both of let-7e-5pb levels (3.55-fold,

更多