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.
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: Biomarkers ; Host-Pathogen Interaction ; Inflammatory response ; Prognostic markers ; Protein Modification ; Serum/Plasma
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Principal Investigators: (in alphabetical order) |
Manuel Mayr, King's British Heart Foundation Centre, King's College London, UK, N/A |
| Submitting User: | ccms |
Cuello F, Shankar-Hari M, Mayr U, Yin X, Marshall M, Suna G, Willeit P, Langley SR, Jayawardhana T, Zeller T, Terblanche M, Shah AM, Mayr M.
Redox state of pentraxin 3 as a novel biomarker for resolution of inflammation and survival in sepsis.
Mol. Cell Proteomics. 2014 Oct;13(10):2545-57. Epub 2014 Jun 23.
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