Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177

Abstract Acute-on-Chronic Liver Failure (ACLF) is associated with innate immune dysfunction and high short-term mortality. Neutrophils have been identified to influence prognosis in ACLF. Neutrophil biology is under-evaluated in ACLF. Therefore, we investigated neutrophil-specific genes and their as...

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Autores principales:	Rohini Saha, Sai Sanwid Pradhan, Shalimar, Prasenjit Das, Priyanka Mishra, Rohan Singh, Venketesh Sivaramakrishnan, Pragyan Acharya
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/60eaeeb26fb4409aaded21b12cc77dda
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spelling	oai:doaj.org-article:60eaeeb26fb4409aaded21b12cc77dda2021-12-02T15:15:04ZInflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD17710.1038/s41598-021-98086-62045-2322https://doaj.org/article/60eaeeb26fb4409aaded21b12cc77dda2021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98086-6https://doaj.org/toc/2045-2322Abstract Acute-on-Chronic Liver Failure (ACLF) is associated with innate immune dysfunction and high short-term mortality. Neutrophils have been identified to influence prognosis in ACLF. Neutrophil biology is under-evaluated in ACLF. Therefore, we investigated neutrophil-specific genes and their association with ACLF outcomes. This is an observational study. Enriched granulocytes, containing neutrophils, isolated from study participants in three groups- ACLF(n = 10), chronic liver disease (CLD, n = 4) and healthy controls (HC, n = 4), were analysed by microarray. Differentially expressed genes were identified and validated by qRT-PCR in an independent cohort of ACLF, CLD and HC (n = 30, 15 and 15 respectively). The association of confirmed overexpressed genes with ACLF 28-day non-survivors was investigated. The protein expression of selected neutrophil genes was confirmed using flow cytometry and IHC. Differential gene expression analysis showed 1140 downregulated and 928 upregulated genes for ACLF versus CLD and 2086 downregulated and 1091 upregulated genes for ACLF versus HC. Significant upregulation of neutrophilic inflammatory signatures were found in ACLF compared to CLD and HC. Neutrophil enriched genes ELANE, MPO and CD177 were highly upregulated in ACLF and their expression was higher in ACLF 28-day non-survivors. Elevated expression of CD177 protein on neutrophil surface in ACLF was confirmed by flow cytometry. IHC analysis in archival post mortem liver biopsies showed the presence of CD177+ neutrophils in the liver tissue of ACLF patients. Granulocyte genes ELANE, MPO and CD177 are highly overexpressed in ACLF neutrophils as compared to CLD or HC. Further, this three-gene signature is highly overexpressed in ACLF 28-day non-survivors.Rohini SahaSai Sanwid PradhanShalimarPrasenjit DasPriyanka MishraRohan SinghVenketesh SivaramakrishnanPragyan AcharyaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rohini Saha Sai Sanwid Pradhan Shalimar Prasenjit Das Priyanka Mishra Rohan Singh Venketesh Sivaramakrishnan Pragyan Acharya Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177
description	Abstract Acute-on-Chronic Liver Failure (ACLF) is associated with innate immune dysfunction and high short-term mortality. Neutrophils have been identified to influence prognosis in ACLF. Neutrophil biology is under-evaluated in ACLF. Therefore, we investigated neutrophil-specific genes and their association with ACLF outcomes. This is an observational study. Enriched granulocytes, containing neutrophils, isolated from study participants in three groups- ACLF(n = 10), chronic liver disease (CLD, n = 4) and healthy controls (HC, n = 4), were analysed by microarray. Differentially expressed genes were identified and validated by qRT-PCR in an independent cohort of ACLF, CLD and HC (n = 30, 15 and 15 respectively). The association of confirmed overexpressed genes with ACLF 28-day non-survivors was investigated. The protein expression of selected neutrophil genes was confirmed using flow cytometry and IHC. Differential gene expression analysis showed 1140 downregulated and 928 upregulated genes for ACLF versus CLD and 2086 downregulated and 1091 upregulated genes for ACLF versus HC. Significant upregulation of neutrophilic inflammatory signatures were found in ACLF compared to CLD and HC. Neutrophil enriched genes ELANE, MPO and CD177 were highly upregulated in ACLF and their expression was higher in ACLF 28-day non-survivors. Elevated expression of CD177 protein on neutrophil surface in ACLF was confirmed by flow cytometry. IHC analysis in archival post mortem liver biopsies showed the presence of CD177+ neutrophils in the liver tissue of ACLF patients. Granulocyte genes ELANE, MPO and CD177 are highly overexpressed in ACLF neutrophils as compared to CLD or HC. Further, this three-gene signature is highly overexpressed in ACLF 28-day non-survivors.
format	article
author	Rohini Saha Sai Sanwid Pradhan Shalimar Prasenjit Das Priyanka Mishra Rohan Singh Venketesh Sivaramakrishnan Pragyan Acharya
author_facet	Rohini Saha Sai Sanwid Pradhan Shalimar Prasenjit Das Priyanka Mishra Rohan Singh Venketesh Sivaramakrishnan Pragyan Acharya
author_sort	Rohini Saha
title	Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177
title_short	Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177
title_full	Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177
title_fullStr	Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177
title_full_unstemmed	Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177
title_sort	inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes elane, mpo and cd177
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/60eaeeb26fb4409aaded21b12cc77dda
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_version_	1718387572307132416

Inflammatory signature in acute-on-chronic liver failure includes increased expression of granulocyte genes ELANE, MPO and CD177

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