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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Transcriptome profiles of peripheral blood mononuclear cells differentiate male adolescents with non-alcoholic fatty liver disease from healthy peers
Natalia Zeber-Lubecka, Jacek Michalkiewicz, Michalina Dabrowska, Krzysztof Goryca, Aldona Wierzbicka-Rucińska, Wojciech Jańczyk, Irena Jankowska, Anna Świąder-Leśniak, Izabela Kubiszewska, Joanna Ziemska-Legięcka, Piotr Socha, Jerzy Ostrowski
Natalia Zeber-Lubecka, Michalina Dabrowska, Krzysztof Goryca, Joanna Ziemska-Legięcka, Jerzy Ostrowski, Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw 02-781, Mazowieckie, Poland
Natalia Zeber-Lubecka, Krzysztof Goryca, Jerzy Ostrowski, Department of Gastroenterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education, Warsaw 02-781, Mazowieckie, Poland
Jacek Michalkiewicz, Department of Microbiology and Clinical Immunology, The Children’s Memorial Health Institute, Warsaw 04-730, Mazowieckie, Poland
Aldona Wierzbicka-Rucińska, Department of Clinical Biochemistry, The Children’s Memorial Health Institute, Warsaw 04-730, Mazowieckie, Poland
Wojciech Jańczyk, Irena Jankowska, Piotr Socha, Department of Gastroenterology, Hepatology and Nutrition Disorders, The Children’s Memorial Health Institute, Warsaw 04-730, Poland
Anna Świąder-Leśniak, Laboratory of Anthropology, The Children’s Memorial Health Institute, Warsaw 04-730, Mazowieckie, Poland
Izabela Kubiszewska, Department of Immunology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Bydgoszcz 85-067, Kujawsko-Pomorskie, Poland
Author contributions: Zeber-Lubecka N, Michalkiewicz J, Dabrowska M, Wierzbicka-Rucińska A, Świąder-Leśniak A, and Kubiszewska I contributed to the investigation; Zeber-Lubecka N, Michalkiewicz J, Goryca K, and Ziemska-Legięcka J contributed to the methodology; Zeber-Lubecka N and Goryca K contributed to visualization and formal analysis; Zeber-Lubecka N and Wierzbicka-Rucińska A contributed to the project administration; Zeber-Lubecka N and Goryca K participated in data curation; Zeber-Lubecka N and Ostrowski J participated in the original manuscript draft; Michalkiewicz J, Socha P, and Ostrowski J contributed to supervision and conceptualization; Jańczyk W, Jankowska I, Świąder-Leśniak A, and Socha P contributed to the resources; Socha P provides funding acquisition; All authors reviewed and edited the manuscript. All authors have read and approved the final manuscript.
Supported by the National Science Centre, No. UMO-2018/31/B/NZ5/02735.
Institutional review board statement: The study was approved by the Ethics Committee of the Children’s Memorial Health Institute in Warsaw, Poland (approval No. 34/KBE/2019).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of this study were deposited at BioProject repository under accession number PRJNA1305173.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jerzy Ostrowski, MD, PhD, Head, Professor, Department of Gastro
enterology, Hepatology and Clinical Oncology, Center of Postgraduate Medical Education, Roentgena 5, Warsaw 02-781, Mazowieckie, Poland.
jostrow@warman.com.pl
Received: August 26, 2025
Revised: September 15, 2025
Accepted: November 10, 2025
Published online: December 27, 2025
Processing time: 125 Days and 22.7 Hours
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.
Core Tip: We studied immune cells from teenage boys with non-alcoholic fatty liver disease and found that their gene activity and immune responses differ from those of healthy peers. These immune-related changes may serve as early indicators of non-alcoholic fatty liver disease and provide insight into its pathogenesis. Our findings highlight the importance of immune profiling in adolescents and may contribute to future strategies for early diagnosis and intervention.
