Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD)
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RESEARCH
Open Access
Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD) Diana Buzova1†, Andrea Maugeri2,3†, Antonio Liguori4†, Cecilia Napodano4†, Oriana Lo Re2, Jude Oben5, Anna Alisi6, Antonio Gasbarrini4, Antonio Grieco4, Jan Cerveny1, Luca Miele4*† and Manlio Vinciguerra1,5*†
Abstract Background: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. Results: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0–33%), 24 patients with steatosis grade 2 (34–66%) and 9 patients with steatosis grade 3 (67–100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. Conclusions: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology. Keywords: Liquid biopsy, Histones, Epigenetics, ImageStream, Metabolic health, Lean MAFLD
* Correspondence: [email protected]; [email protected] † Diana Buzova, Andrea Maugeri, Antonio Liguori and Cecilia Napodano contributed equally to this work. 4 Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy 1 Department of Adaptive Biotechnologies, Global Change Research Institute CAS, Brno, Czech Republic Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in t
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