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

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

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

Buzova, D Maugeri, A Liguori, A Napodano, C Lo Re, O Oben, J Alisi, A Gasbarrini, A Grieco, A Cerveny, J

Miele, L Vinciguerra, M

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Publisher:: BMC
Publication Type:: Journal Article
Citation:: Clinical epigenetics, 2020, 12, (1), pp. 126
Issue Date:: 2020-08-20

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Field	Value	Language
dc.contributor.author	Buzova, D
dc.contributor.author	Maugeri, A
dc.contributor.author	Liguori, A
dc.contributor.author	Napodano, C
dc.contributor.author	Lo Re, O
dc.contributor.author	Oben, J
dc.contributor.author	Alisi, A
dc.contributor.author	Gasbarrini, A
dc.contributor.author	Grieco, A
dc.contributor.author	Cerveny, J https://orcid.org/0000-0002-5046-3105
dc.contributor.author	Miele, L
dc.contributor.author	Vinciguerra, M
dc.date.accessioned	2020-11-08T18:51:27Z
dc.date.available	2020-08-13
dc.date.available	2020-11-08T18:51:27Z
dc.date.issued	2020-08-20
dc.identifier.citation	Clinical epigenetics, 2020, 12, (1), pp. 126
dc.identifier.issn	1868-7075
dc.identifier.issn	1868-7083
dc.identifier.uri	http://hdl.handle.net/10453/143848
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	BMC
dc.relation.ispartof	Clinical epigenetics
dc.relation.isbasedon	10.1186/s13148-020-00917-2
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	0604 Genetics, 1103 Clinical Sciences, 1114 Paediatrics and Reproductive Medicine
dc.title	Circulating histone signature of human lean metabolic-associated fatty liver disease (MAFLD).
dc.type	Journal Article
utslib.citation.volume	12
utslib.location.activity	Germany
utslib.for	0604 Genetics
utslib.for	1103 Clinical Sciences
utslib.for	1114 Paediatrics and Reproductive Medicine
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2020-11-08T18:51:18Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	12
utslib.citation.issue	1

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.

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http://hdl.handle.net/10453/143848