Redox State of Pentraxin 3 as a Novel Biomarker for Resolution of Inflammation and Survival in Sepsis

TY - JOUR

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

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 lungcommon 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 lungcommon 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.

KW - C-REACTIVE PROTEIN

KW - AMYLOID-P COMPONENT

KW - ENDOTHELIAL-CELLS

KW - INNATE IMMUNITY

KW - PROTEOMICS

KW - PTX3

KW - FAMILY

KW - SIMILARITIES

KW - RECOGNITION

KW - DISEASE

UR - http://www.scopus.com/inward/record.url?scp=84907960573&partnerID=8YFLogxK

U2 - 10.1074/mcp.M114.039446

DO - 10.1074/mcp.M114.039446

M3 - Article

AN - SCOPUS:84907960573

SN - 1535-9476

VL - 13

SP - 2545

EP - 2557

JO - MOLECULAR AND CELLULAR PROTEOMICS

JF - MOLECULAR AND CELLULAR PROTEOMICS

IS - 10

ER -