Proteomics

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Redox-state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis


ABSTRACT: 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. PTX3 accumulated as an octamer due to disulphide-bond formation in heart, kidney and lung ?common organ dysfunctions seen in patients with sepsis. Oligomeric moieties of PTX3 were also detectable in the circulation. The redox-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 redox-state of PTX3 between survivors and non-survivors. From day 2 onwards, 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 undetectable in survivors, but still constituted more than half of total PTX3 in non-survivors (P<0.001). Monomeric PTX3 was inversely associated with cardiac damage markers NT-proBNP, high sensitivity troponin I and T. In comparison to the conventional measurements of total PTX3 or NT-proBNP, the redox-sensitive oligomerization of PTX3 was more dynamic and a superior predictor of disease outcome.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Manuel Mayr  

PROVIDER: MSV000081708 | MassIVE | Fri Nov 10 15:30:00 GMT 2017

SECONDARY ACCESSION(S): PXD001020

REPOSITORIES: MassIVE

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Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis.

Cuello Friederike F   Shankar-Hari Manu M   Mayr Ursula U   Yin Xiaoke X   Marshall Melanie M   Suna Gonca G   Willeit Peter P   Langley Sarah R SR   Jayawardhana Tamani T   Zeller Tanja T   Terblanche Marius M   Shah Ajay M AM   Mayr Manuel M  

Molecular & cellular proteomics : MCP 20140623 10


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 oligomerizati  ...[more]

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