Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis
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Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis. / Cuello, Friederike; Shankar-Hari, Manu; Mayr, Ursula; Yin, Xiaoke; Marshall, Melanie; Suna, Gonca; Willeit, Peter; Langley, Sarah R; Jayawardhana, Tamani; Zeller, Tanja; Terblanche, Marius; Shah, Ajay M; Mayr, Manuel.
In: MOL CELL PROTEOMICS, Vol. 13, No. 10, 01.10.2014, p. 2545-57.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis
AU - Cuello, Friederike
AU - Shankar-Hari, Manu
AU - Mayr, Ursula
AU - Yin, Xiaoke
AU - Marshall, Melanie
AU - Suna, Gonca
AU - Willeit, Peter
AU - Langley, Sarah R
AU - Jayawardhana, Tamani
AU - Zeller, Tanja
AU - Terblanche, Marius
AU - Shah, Ajay M
AU - Mayr, Manuel
N1 - © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2014/10/1
Y1 - 2014/10/1
N2 - In an endotoxaemic mouse model of sepsis, a tissue-based proteomics approach for biomarker discovery identified long pentraxin 3 (PTX3) as the lead candidate for inflamed myocardium. When the redox-sensitive oligomerization state of PTX3 was further investigated, PTX3 accumulated as an octamer as a result of disulfide-bond formation in heart, kidney, and lung-common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in circulation. The oligomerization state of PTX3 was quantified over the first 11 days in critically ill adult patients with sepsis. On admission day, there was no difference in the oligomerization state of PTX3 between survivors and non-survivors. From day 2 onward, the conversion of octameric to monomeric PTX3 was consistently associated with a greater survival after 28 days of follow-up. For example, by day 2 post-admission, octameric PTX3 was barely detectable in survivors, but it still constituted more than half of the total PTX3 in non-survivors (p < 0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP and high-sensitivity troponin I and T. Relative to the conventional measurements of total PTX3 or NT-proBNP, the oligomerization of PTX3 was a superior predictor of disease outcome.
AB - In an endotoxaemic mouse model of sepsis, a tissue-based proteomics approach for biomarker discovery identified long pentraxin 3 (PTX3) as the lead candidate for inflamed myocardium. When the redox-sensitive oligomerization state of PTX3 was further investigated, PTX3 accumulated as an octamer as a result of disulfide-bond formation in heart, kidney, and lung-common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in circulation. The oligomerization state of PTX3 was quantified over the first 11 days in critically ill adult patients with sepsis. On admission day, there was no difference in the oligomerization state of PTX3 between survivors and non-survivors. From day 2 onward, the conversion of octameric to monomeric PTX3 was consistently associated with a greater survival after 28 days of follow-up. For example, by day 2 post-admission, octameric PTX3 was barely detectable in survivors, but it still constituted more than half of the total PTX3 in non-survivors (p < 0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP and high-sensitivity troponin I and T. Relative to the conventional measurements of total PTX3 or NT-proBNP, the oligomerization of PTX3 was a superior predictor of disease outcome.
U2 - 10.1074/mcp.M114.039446
DO - 10.1074/mcp.M114.039446
M3 - SCORING: Journal article
C2 - 24958171
VL - 13
SP - 2545
EP - 2557
JO - MOL CELL PROTEOMICS
JF - MOL CELL PROTEOMICS
SN - 1535-9476
IS - 10
ER -
