Transcriptome profiles of peripheral blood mononuclear cells differentiate male adolescents with non-alcoholic fatty liver disease from healthy peers.
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BACKGROUND: Numerous studies have reported specific expression profiles of peripheral blood mononuclear cells (PBMCs) that are associated with infectious, autoimmune, and inflammatory disorders, including chronic liver diseases. AIM: To identify potential differences in the transcriptome profiles of PBMCs between male patients with non-alcoholic fatty liver disease (NAFLD) and healthy male adolescents. METHODS: PBMCs were isolated from 16 male adolescents with NAFLD and 14 healthy age-matched male peers. The collected cells were cultured in vitro for 18 hours without and with autologous fecal extracts (FEs). Differentially expressed genes (DEGs) were investigated using RNA sequencing. Levels of interleukin (IL)-6, tumor necrosis factor-α, IL-10, and IL-1β secreted into the culture medium were determined using enzyme-linked immunosorbent assays. DEGs were functionally analyzed through annotation according to the Gene Ontology and Reactome databases. RESULTS: In total, 151 (118 protein-coding) and 97 (65 protein-coding) DEGs were identified when the RNA profiles of PBMCs stimulated without and with FEs, respectively, were compared between NAFLD patients and controls. Functional enrichment analysis of DEGs identified several pathways, which were predominantly involved in metabolism and inflammatory responses in non-stimulated and FE-stimulated PBMCs, respectively. FEs increased secretion of IL-6 and IL-1β by PBMCs isolated from controls and of all four cytokines by PBMCs isolated from NAFLD patients. IL-1β secretion was significantly higher in FE-stimulated PBMCs isolated from NAFLD patients than in those isolated from controls. CONCLUSION: Our data suggest that changes in PBMC gene expression may provide candidate biomarkers for NAFLD development, which require validation in larger cohorts.