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Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD)

D. Buzova, A. Maugeri, A. Liguori, C. Napodano, O. Lo Re, J. Oben, A. Alisi, A. Gasbarrini, A. Grieco, J. Cerveny, L. Miele, M. Vinciguerra

. 2020 ; 12 (1) : 126. [pub] 20200820

Language English Country Germany

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc22004866

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.

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$a BACKGROUND: Although metabolic associate fatty liver disease (MAFLD) is associated with obesity, it can also occur in lean patients. MAFLD is more aggressive in lean patients compared to obese patients, with a higher risk of mortality. Specific biomarkers to diagnose differentially lean or overweight MAFLD are missing. Histones and nucleosomes are released in the bloodstream upon cell death. Here, we propose a new, fast, imaging and epigenetics based approach to investigate the severity of steatosis in lean MAFLD patients. RESULTS: A total of 53 non-obese patients with histologically confirmed diagnosis of MAFLD were recruited. Twenty patients displayed steatosis grade 1 (0-33%), 24 patients with steatosis grade 2 (34-66%) and 9 patients with steatosis grade 3 (67-100%). The levels of circulating nucleosomes were assayed using enzyme-linked immunosorbent assay, while individual histones or histone dimers were assayed in serum samples by means of a new advanced flow cytometry ImageStream(X)-adapted method. Circulating nucleosome levels associated poorly with MAFLD in the absence of obesity. We implemented successfully a multi-channel flow methodology on ImageStream(X), to image single histone staining (H2A, H2B, H3, H4, macroH2A1.1 and macroH2A1.2). We report here a significant depletion of the levels of histone variants macroH2A1.1 and macroH2A1.2 in the serum of lean MAFLD patients, either individually or in complex with H2B. CONCLUSIONS: In summary, we identified a new circulating histone signature able to discriminate the severity of steatosis in individuals with lean MAFLD, using a rapid and non-invasive ImageStream(X)-based imaging technology.
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$a Maugeri, Andrea $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic $u Department of Medical and Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Catania, Italy
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$a Liguori, Antonio $u Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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$a Napodano, Cecilia $u Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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$a Lo Re, Oriana $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic
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$a Oben, Jude $u Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK
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$a Alisi, Anna $u Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy
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$a Gasbarrini, Antonio $u Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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$a Grieco, Antonio $u Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
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$a Cerveny, Jan $u Department of Adaptive Biotechnologies, Global Change Research Institute CAS, Brno, Czech Republic
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$a Miele, Luca $u Department of Gastroenterological, Endocrine-Metabolic and Nephro-Urological Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. luca.miele@policlinicogemelli.it
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$a Vinciguerra, Manlio $u International Clinical Research Center, St Anne's University Hospital, Brno, Czech Republic. manlio.vinciguerra@fnusa.cz $u Institute for Liver and Digestive Health, Division of Medicine, University College London, London, UK. manlio.vinciguerra@fnusa.cz
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