title: 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. 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.
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK; §Department of Experimental Pharmacology and Toxicology, Cardiovascular Research Centre, University Medical Center Hamburg-Eppendorf, Hamburg, 20246 Germany; ¶DZHK (German Center for Cardiovascular Research), partner site Hamburg/Kiel/Lübeck, Germany;
authors: Friederike
authors: F
authors: Cuello
authors: ‖Critical Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH UK; **Division of Asthma Allergy and Lung Biology, King's College, London SE1 9RT, UK;
authors: Manu
authors: M
authors: Shankar-Hari
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK;
authors: Ursula
authors: U
authors: Mayr
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK;
authors: Xiaoke
authors: X
authors: Yin
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK;
authors: Melanie
authors: M
authors: Marshall
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK;
authors: Gonca
authors: G
authors: Suna
authors: ‡‡Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; §§Department of Neurology, Innsbruck Medical University, Innsbruck, 6020 Austria;
authors: Peter
authors: P
authors: Willeit
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK;
authors: Sarah R
authors: SR
authors: Langley
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK;
authors: Tamani
authors: T
authors: Jayawardhana
authors: ¶¶Clinic for General and Interventional Cardiology, University Heart Centre Hamburg, Hamburg 20246, Germany.
authors: Tanja
authors: T
authors: Zeller
authors: ‖Critical Care Medicine, Guy's and St Thomas' NHS Foundation Trust, London, SE1 7EH UK;
authors: Marius
authors: M
authors: Terblanche
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK;
authors: Ajay M
authors: AM
authors: Shah
authors: From the ‡King's British Heart Foundation Centre, King's College London, SE5 9NU London, UK; manuel.mayr@kcl.ac.uk.
authors: Manuel
authors: M
authors: Mayr
mesh_terms: D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D002097:C-Reactive Protein / Q000737:chemistry* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010084:Oxidation-Reduction; D011379:Prognosis; D055503:Protein Multimerization; D040901:Proteomics / Q000379:methods*; D018805:Sepsis / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000683:Serum Amyloid P-Component / Q000737:chemistry* / Q000378:metabolism*; D000099153:Pentraxins
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D000683:Serum Amyloid P-Component; D000099153:Pentraxins