Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.

<h4>Objectives</h4>In alcoholic hepatitis (AH), dysfunctional T lymphocytes may contribute to the high mortality from infections. T lymphocyte activation is governed by the expression of co-stimulatory receptors such as 4-1BB balanced by inhibitory receptors such as Programmed Death rece...

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Auteurs principaux:	Lotte Lindgreen Eriksen, Morten Aagaard Nielsen, Tea Lund Laursen, Bent Deleuran, Hendrik Vilstrup, Sidsel Støy
Format:	article
Langue:	EN
Publié:	Public Library of Science (PLoS) 2021
Sujets:	Medicine R Science Q
Accès en ligne:	https://doaj.org/article/b6061a0c7b9a45bf8a299b67b9d94eab
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spelling	oai:doaj.org-article:b6061a0c7b9a45bf8a299b67b9d94eab2021-12-02T20:18:37ZEarly loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.1932-620310.1371/journal.pone.0255574https://doaj.org/article/b6061a0c7b9a45bf8a299b67b9d94eab2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0255574https://doaj.org/toc/1932-6203<h4>Objectives</h4>In alcoholic hepatitis (AH), dysfunctional T lymphocytes may contribute to the high mortality from infections. T lymphocyte activation is governed by the expression of co-stimulatory receptors such as 4-1BB balanced by inhibitory receptors such as Programmed Death receptor 1 (PD-1). 4-1BB expression is unaccounted for in AH, while PD-1 is elevated. We characterized expression of 4-1BB and PD-1 and the associated T lymphocyte functional status in AH and investigated whether these were associated with short-term mortality.<h4>Methods</h4>Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and in vitro stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA.<h4>Results</h4>At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4+ T lymphocytes. Also, the frequencies of PD-1+ T lymphocytes both with and without co-expressed 4-1BB were increased. Further, interferon-gamma was predominantly produced in T lymphocytes co-expressing 4-1BB. A decrease in the frequency of spontaneous 4-1BB+ T lymphocytes and an increase in soluble 4-1BB during the first week after diagnosis were associated with higher mortality at day 90 in AH. PD-1 expression showed no systematic dynamics related to mortality.<h4>Conclusions</h4>We found an increased stimulated 4-1BB response of T lymphocytes in AH and early loss of these lymphocytes was associated with a higher short-term mortality. This suggests a role of T lymphocyte 4-1BB expression in the progression of AH.Lotte Lindgreen EriksenMorten Aagaard NielsenTea Lund LaursenBent DeleuranHendrik VilstrupSidsel StøyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 8, p e0255574 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lotte Lindgreen Eriksen Morten Aagaard Nielsen Tea Lund Laursen Bent Deleuran Hendrik Vilstrup Sidsel Støy Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
description	<h4>Objectives</h4>In alcoholic hepatitis (AH), dysfunctional T lymphocytes may contribute to the high mortality from infections. T lymphocyte activation is governed by the expression of co-stimulatory receptors such as 4-1BB balanced by inhibitory receptors such as Programmed Death receptor 1 (PD-1). 4-1BB expression is unaccounted for in AH, while PD-1 is elevated. We characterized expression of 4-1BB and PD-1 and the associated T lymphocyte functional status in AH and investigated whether these were associated with short-term mortality.<h4>Methods</h4>Thirty-five patients with AH (at diagnosis and days 7 and 90) were compared with healthy controls (HC). Spontaneous and in vitro stimulated receptor expression were quantified by flow cytometry, and plasma proteins by ELISA.<h4>Results</h4>At diagnosis, the patients showed increased stimulated 4-1BB responses of CD4+ T lymphocytes. Also, the frequencies of PD-1+ T lymphocytes both with and without co-expressed 4-1BB were increased. Further, interferon-gamma was predominantly produced in T lymphocytes co-expressing 4-1BB. A decrease in the frequency of spontaneous 4-1BB+ T lymphocytes and an increase in soluble 4-1BB during the first week after diagnosis were associated with higher mortality at day 90 in AH. PD-1 expression showed no systematic dynamics related to mortality.<h4>Conclusions</h4>We found an increased stimulated 4-1BB response of T lymphocytes in AH and early loss of these lymphocytes was associated with a higher short-term mortality. This suggests a role of T lymphocyte 4-1BB expression in the progression of AH.
format	article
author	Lotte Lindgreen Eriksen Morten Aagaard Nielsen Tea Lund Laursen Bent Deleuran Hendrik Vilstrup Sidsel Støy
author_facet	Lotte Lindgreen Eriksen Morten Aagaard Nielsen Tea Lund Laursen Bent Deleuran Hendrik Vilstrup Sidsel Støy
author_sort	Lotte Lindgreen Eriksen
title	Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
title_short	Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
title_full	Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
title_fullStr	Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
title_full_unstemmed	Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
title_sort	early loss of t lymphocyte 4-1bb receptor expression is associated with higher short-term mortality in alcoholic hepatitis.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/b6061a0c7b9a45bf8a299b67b9d94eab
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Early loss of T lymphocyte 4-1BB receptor expression is associated with higher short-term mortality in alcoholic hepatitis.

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