Circulating RIPK3 levels are associated with mortality and organ failure during critical illness

JCI Insight
Kevin C MaAugustine Mk Choi

Abstract

Necroptosis is a form of programmed necrotic cell death that is rapidly emerging as an important pathophysiological pathway in numerous disease states. Necroptosis is dependent on receptor-interacting protein kinase 3 (RIPK3), a protein shown to play an important role in experimental models of critical illness. However, there is limited clinical evidence regarding the role of extracellular RIPK3 in human critical illness. Plasma RIPK3 levels were measured in 953 patients prospectively enrolled in 5 ongoing intensive care unit (ICU) cohorts in both the USA and Korea. RIPK3 concentrations among groups were compared using prospectively collected phenotypic and outcomes data. In all 5 cohorts, extracellular RIPK3 levels in the plasma were higher in patients who died in the hospital compared with those who survived to discharge. In a combined analysis, increasing RIPK3 levels were associated with elevated odds of in-hospital mortality (odds ratio [OR] 1.7 for each log10-unit increase in RIPK3 level, P < 0.0001). When adjusted for baseline severity of illness, the OR for in-hospital mortality remained statistically significant (OR 1.33, P = 0.007). Higher RIPK3 levels were also associated with more severe organ failure. Our findings ...Continue Reading

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Citations

Nov 28, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Hilary Faust, Nilam S Mangalmurti
Jul 9, 2020·Journal of Cellular and Molecular Medicine·Yunjoo ImKyeongman Jeon
Aug 9, 2019·JCI Insight·Mary E ChoiAugustine M K Choi
Dec 7, 2018·JCI Insight·Laura E FredenburghAugustine Mk Choi
Aug 25, 2020·International Journal of Environmental Research·Walter Gottlieb Land
Jun 30, 2019·Critical Care : the Official Journal of the Critical Care Forum·Michael G S ShashatyNilam S Mangalmurti
Aug 3, 2020·Life Sciences·Gerwyn MorrisMichael Berk
Apr 1, 2021·Cellular & Molecular Immunology·Damien BerthelootBernardo S Franklin
Nov 28, 2020·The European Respiratory Journal·Soo Jung ChoHeather Stout-Delgado
Oct 15, 2021·Scientific Reports·Yunjoo ImKyeongman Jeon

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Methods Mentioned

BETA
blood collection
enzyme-linked immunosorbent assay

Software Mentioned

R Foundation for Statistical Computing
R

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