Gene and miRNA expression profiles in peripheral blood mononuclear cells (PBMCs) and sputum samples from patients with COPD with and without PiZZ- alpha1 antitrypsin deficiency

<bold>Introduction:</bold> COPD has complex etiologies. Among genetic determinants, the most recognized is a severe PiZZ (Glu342Lys) inherited alpha1-antitrypsin deficiency (AATD). We performed a gene expression profiling of blood cells and sputum collected from mild and severe COPD with and without PiZZ AATD in order to carry out an integrative analysis to find a molecular signature of disease severity. <bold>Methods:</bold> Peripheral blood mononuclear cells(PBMC) and sputum from 7 PiZZ AATD,17 COPD FEV1>=50% and 16 COPD FEV1<50% were included in this high-throughput microarray study. We compared the cellular expression of RNA and miRNA in blood and sputum of the 3 groups and performed functional and enrichment analyses using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene-ontology (GO) terms. <bold>Results:</bold> The 3 groups were similar in age, gender, previous exac­erbations and comorbidities. PIZZ AATD patients presented a gene expresion pattern similar to the mild COPD group. The biggest differences were found comparing the severe vs. mild COPD patients. A total of 134 and 373 differentially expressed (DE) genes (p<0.05 and log FC>0.5) were respectively identified in blood and sputum. These genes are involved in Slit/Robo, interleukin and death receptor signaling. In addition, a total of 40 and 12 DE miRNAs were identified in blood and sputum that regulate target genes involved in MAPK cascade and VEGFA-VEGFR2 signaling. We observed a high concordance between the results observed in blood and sputum samples. <bold>Conclusions:</bold> we identified the activation of pathways related to inflammation and angiogenesis, apoptosis, tumor cell migration and metastasis comparing patients with severe vs mild COPD and severe COPD-AATD. Gene expression pattern observed from sputum cells was similar to that observed in PBMC.