Circulating microRNAs as potential biomarkers in alpha-1 antitrypsin deficiency patients

Background: Alpha-1 antitrypsin deficiency (AATD) is a hereditary condition that leads to decreased circulating AAT levels, significantly increasing the risk of serious lung and liver disease in children and adults. AATD is a highly under-diagnosed condition and shows a high degree of variability. AAT serum levels and phenotype are not enough to identify those patients that will develop severe lung or liver pathology. Rationale and aims : MicroRNAs (miRNAs) regulate gene expression and have been associated with the pathogenesis of several lung and liver diseases. Cell-free circulating miRNAs may serve as diagnostic biomarkers of AATD but the miRNAs profile in AATD is currently unknown. This study is aimed to find a plasma miRNA expression profile in AATD that can assist diagnosis. Methods : Thirty children with AATD were prospectively included in the study. Patients were classified in three risk groups of developing lung disease: low (MM; MS; SS phenotypes), intermediate (MZ; SZ) and high risk (ZZ). Plasma miRNA expression profiling was performed by using GeneChip miRNA 3.0 Arrays (Affymetrix). Differentially expressed miRNAs were validated by qRT-PCR. Results : A profile of 32 plasma miRNAs, which can potentially serve as biomarkers for AATD, was found. These miRNAs were validated in 145 patients with AATD and 9 miRNAs were found to be significantly deregulated, which can potentially serve as biomarkers for AATD diagnosis. Conclusions :The analysis of plasma miRNAs profile in AATD individuals has established a genetic signature that differentiates the different risk groups. Therefore, miRNA expression analysis may open new ways of diagnosing and monitoring lung and liver damage associated to AATD.