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

0531871 - ÚVGZ 2021 RIV GB eng J - Journal Article
Búzová, Diana - Maugeri, A. - Liguori, A. - Napodano, C. - Lo Re, O. - Oben, J. - Alisi, A. - Gasbarrini, A. - Grieco, A. - Červený, Jan - Miele, L. - Vinciguerra, M.
Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).
Clinical Epigenetics. Roč. 12, č. 1 (2020), č. článku 126. ISSN 1868-7075. E-ISSN 1868-7083
R&D Projects: GA MZd(CZ) NV18-03-00058
Research Infrastructure: CzeCOS III - 90123
Institutional support: RVO:86652079
Keywords : Epigenetics * Histones * ImageStream * Lean MAFLD * Liquid biopsy * Metabolic health
OECD category: Endocrinology and metabolism (including diabetes, hormones)
Impact factor: 6.551, year: 2020
Method of publishing: Open access
https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-020-00917-2

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.
Permanent Link: http://hdl.handle.net/11104/0310512