Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes

Abstract The role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1...

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Autores principales:	Hongseok Yoo, Yunjoo Im, Ryoung-Eun Ko, Jin Young Lee, Junseon Park, Kyeongman Jeon
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0a3218336d134e7480d501b1327c56ea
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spelling	oai:doaj.org-article:0a3218336d134e7480d501b1327c56ea2021-12-02T15:37:58ZAssociation of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes10.1038/s41598-021-88970-62045-2322https://doaj.org/article/0a3218336d134e7480d501b1327c56ea2021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88970-6https://doaj.org/toc/2045-2322Abstract The role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1 and the severity and clinical outcomes of sepsis, and to examine the correlation between HMGB1 and key executors of necroptosis including receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like- (MLKL) proteins. Plasma HMGB1, RIPK3, and MLKL levels were measured with the enzyme-linked immunosorbent assay from the derivation cohort of 188 prospectively enrolled, critically-ill patients between April 2014 and December 2016, and from the validation cohort of 77 patients with sepsis between January 2017 and January 2019. In the derivation cohort, the plasma HMGB1 levels of the control (n = 46, 24.5%), sepsis (n = 58, 30.9%), and septic shock (n = 84, 44.7%) groups were significantly increased (P < 0.001). A difference in mortality between high (≥ 5.9 ng/mL) and low (< 5.9 ng/mL) HMGB1 levels was observed up to 90 days (Log-rank test, P = 0.009). There were positive linear correlations of plasma HMGB1 with RIPK3 (R2 = 0.61, P < 0.001) and MLKL (R2 = 0.7890, P < 0.001). The difference in mortality and correlation of HMGB1 levels with RIPK3 and MLKL were confirmed in the validation cohort. Plasma levels of HMGB1 were associated with the severity and mortality attributed to sepsis. They were correlated with RIPK3 and MLKL, thus suggesting an association of HMGB1 with necroptosis.Hongseok YooYunjoo ImRyoung-Eun KoJin Young LeeJunseon ParkKyeongman JeonNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hongseok Yoo Yunjoo Im Ryoung-Eun Ko Jin Young Lee Junseon Park Kyeongman Jeon Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
description	Abstract The role of high-mobility group box-1 (HMGB1) in outcome prediction in sepsis is controversial. Furthermore, its association with necroptosis, a programmed cell necrosis mechanism, is still unclear. The purpose of this study is to identify the association between the plasma levels of HMGB1 and the severity and clinical outcomes of sepsis, and to examine the correlation between HMGB1 and key executors of necroptosis including receptor-interacting kinase 3 (RIPK3) and mixed lineage kinase domain-like- (MLKL) proteins. Plasma HMGB1, RIPK3, and MLKL levels were measured with the enzyme-linked immunosorbent assay from the derivation cohort of 188 prospectively enrolled, critically-ill patients between April 2014 and December 2016, and from the validation cohort of 77 patients with sepsis between January 2017 and January 2019. In the derivation cohort, the plasma HMGB1 levels of the control (n = 46, 24.5%), sepsis (n = 58, 30.9%), and septic shock (n = 84, 44.7%) groups were significantly increased (P < 0.001). A difference in mortality between high (≥ 5.9 ng/mL) and low (< 5.9 ng/mL) HMGB1 levels was observed up to 90 days (Log-rank test, P = 0.009). There were positive linear correlations of plasma HMGB1 with RIPK3 (R2 = 0.61, P < 0.001) and MLKL (R2 = 0.7890, P < 0.001). The difference in mortality and correlation of HMGB1 levels with RIPK3 and MLKL were confirmed in the validation cohort. Plasma levels of HMGB1 were associated with the severity and mortality attributed to sepsis. They were correlated with RIPK3 and MLKL, thus suggesting an association of HMGB1 with necroptosis.
format	article
author	Hongseok Yoo Yunjoo Im Ryoung-Eun Ko Jin Young Lee Junseon Park Kyeongman Jeon
author_facet	Hongseok Yoo Yunjoo Im Ryoung-Eun Ko Jin Young Lee Junseon Park Kyeongman Jeon
author_sort	Hongseok Yoo
title	Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
title_short	Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
title_full	Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
title_fullStr	Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
title_full_unstemmed	Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
title_sort	association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0a3218336d134e7480d501b1327c56ea
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Association of plasma level of high-mobility group box-1 with necroptosis and sepsis outcomes

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