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

Diana Buzova, Andrea Maugeri, Antonio Liguori, Cecilia Napodano, Oriana Lo Re, Jude Oben, Anna Alisi, Antonio Gasbarrini, Antonio Grieco, Jan Cerveny, Luca Miele, Manlio Vinciguerra

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number126
JournalClinical Epigenetics
Volume12
Issue number1
DOIs
Publication statusPublished - Aug 20 2020

Keywords

  • Epigenetics
  • Histones
  • ImageStream
  • Lean MAFLD
  • Liquid biopsy
  • Metabolic health

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Developmental Biology
  • Genetics(clinical)

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