title: Pentraxin-3 serum levels are associated with disease severity and mortality in patients with systemic inflammatory response syndrome.
abstract: The long pentraxin-3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to pro-inflammatory stimuli. To investigate PTX3 levels and its use as a biomarker in patients with systemic inflammation, we developed a solid-phase enzyme-linked immunosorbent assay based on novel anti-PTX3 monoclonal antibodies detecting PTX3 with high sensitivity. The assay was applied on 261 consecutive patients admitted to an intensive care unit prospectively monitored with the systemic inflammatory response syndrome (SIRS). 100 blood donors were included as controls. PTX3 levels were elevated in patients (median = 71.3 ng/ml) compared with the controls (median = 0 ng/ml) (Mann-Whitney, p<0.0001). ROC analysis showed that PTX3 levels were significantly specific (85.0%) and sensitive (89.1%) to discriminate between healthy controls and patients (area under the curve (AUC) 0.922 (95% CI 0.892 to 0.946, p<0.0001)). Higher levels of PTX3 were associated with the development of sepsis, severe sepsis and septic shock (p = 0.0001). The serum levels of PTX3 correlated significantly with SAPS2 score (Spearman's rho 0.28, p<0.0001). Patients with high levels of PTX3 at admission did have a higher 90 day mortality rate than patients with the 25% lowest levels (Cox regression analysis, hazard ratio 3.0, p = 0.0009). In conclusion, we have established a highly sensitive and robust assay for measurement of PTX3 and found that its serum concentrations correlated with disease severity and mortality in patients with SIRS and sepsis.
authors.affiliation: Laboratory of Molecular Medicine, Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Simone
authors.initials: S
authors.lastname: Bastrup-Birk
authors.forename: Mikkel-Ole
authors.initials: MO
authors.lastname: Skjoedt
authors.forename: Lea
authors.initials: L
authors.lastname: Munthe-Fog
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Strom
authors.forename: Ying Jie
authors.initials: YJ
authors.lastname: Ma
authors.forename: Peter
authors.initials: P
authors.lastname: Garred
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012372:ROC Curve; D011994:Recombinant Proteins / Q000378:metabolism; D012016:Reference Values; D018805:Sepsis / Q000097:blood / Q000401:mortality; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood / Q000401:mortality; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000401:mortality*; D055815:Young Adult; D000099153:Pentraxins
chemical_list: D015415:Biomarkers; D002097:C-Reactive Protein; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
references.citation: Crit Care Med. 2001 Jul;29(7):1404-7
references.pmid: 11445697
references.citation: PLoS One. 2013;8(1):e53661
references.pmid: 23341967
references.citation: Annu Rev Immunol. 2010;28:157-83
references.pmid: 19968561
references.citation: Curr Mol Med. 2010 Mar;10(2):227-35
references.pmid: 20196725
references.citation: Circulation. 2004 Oct 19;110(16):2349-54
references.pmid: 15477419
references.citation: J Exp Med. 2007 Apr 16;204(4):793-804
references.pmid: 17389238
references.citation: Am J Med. 2004 Mar 22;116 Suppl 6A:9S-16S
references.pmid: 15050187
references.citation: Chest. 1992 Jun;101(6):1644-55
references.pmid: 1303622
references.citation: J Clin Immunol. 2012 Apr;32(2):330-9
references.pmid: 22173877
references.citation: Adv Exp Med Biol. 2009;653:98-116
references.pmid: 19799114
references.citation: J Biol Chem. 1997 Dec 26;272(52):32817-23
references.pmid: 9407058
references.citation: Crit Care. 2008;12(3):R83
references.pmid: 18577209
references.citation: Nature. 1975 Aug 7;256(5517):495-7
references.pmid: 1172191
references.citation: Adv Exp Med Biol. 2012;946:1-20
references.pmid: 21948359
references.citation: Tissue Antigens. 2011 Apr;77(4):271-82
references.pmid: 21388349
references.citation: Crit Care Med. 2001 Jul;29(7):1303-10
references.pmid: 11445675
references.citation: J Infect Dis. 2003 Nov 1;188(9):1394-403
references.pmid: 14593599
references.citation: PLoS One. 2011 Mar 10;6(3):e17653
references.pmid: 21423699
references.citation: Immunobiology. 2012 May;217(5):483-91
references.pmid: 21601307
references.citation: Intensive Care Med. 2010 Apr;36(4):621-9
references.pmid: 20119647
references.citation: Arterioscler Thromb Vasc Biol. 2007 Jan;27(1):161-7
references.pmid: 17095712
references.citation: Crit Care Med. 2003 Apr;31(4):1250-6
references.pmid: 12682500
references.citation: Annu Rev Immunol. 2005;23:337-66
references.pmid: 15771574
references.citation: Immunobiology. 2012 Nov;217(11):1122-8
references.pmid: 22964239
references.citation: Clin Chem Lab Med. 2009;47(4):471-7
references.pmid: 19327124
references.citation: Mol Immunol. 2007 Jan;44(4):401-11
references.pmid: 16595153
references.citation: J Clin Immunol. 2008 Jan;28(1):1-13
references.pmid: 17828584
references.citation: Expert Rev Anti Infect Ther. 2012 Jun;10(6):701-6
references.pmid: 22734959
references.citation: Dis Markers. 2009;27(3):157-72
references.pmid: 19893210
references.citation: JAMA. 1993 Dec 22-29;270(24):2957-63
references.pmid: 8254858
references.citation: Intensive Care Med. 2000;26 Suppl 1:S64-74
references.pmid: 10786961