Pentraxin 3 (PTX3) Is Associated with Severe Sepsis and Fatal Disease in Emergency Room Patients with Suspected Infection: A Prospective Cohort Study

Abstract

BackgroundEarly diagnostic and prognostic stratification of patients with suspected infection is a difficult clinical challenge. We studied plasma pentraxin 3 (PTX3) upon admission to the emergency department in patients with suspected infection.MethodsThe study comprised 537 emergency room patients with suspected infection: 59 with no systemic inflammatory response syndrome (SIRS) and without bacterial infection (group 1), 67 with bacterial infection without SIRS (group 2), 54 with SIRS without bacterial infection (group 3), 308 with sepsis (SIRS and bacterial infection) without organ failure (group 4) and 49 with severe sepsis (group 5). Plasma PTX3 was measured on admission using a commercial solid-phase enzyme-linked immunosorbent assay (ELISA).ResultsThe median PTX3 levels in groups 1–5 were 2.6 ng/ml, 4.4 ng/ml, 5.0 ng/ml, 6.1 ng/ml and 16.7 ng/ml, respectively (p<0.001). The median PTX3 concentration was higher in severe sepsis patients compared to others (16.7 vs. 4.9 ng/ml, p<0.001) and in non-survivors (day 28 case fatality) compared to survivors (14.1 vs. 5.1 ng/ml, p<0.001). A high PTX3 level predicted the need for ICU stay (p<0.001) and hypotension (p<0.001). AUCROC in the prediction of severe sepsis was 0.73 (95% CI 0.66–0.81, p<0.001) and 0.69 in case fatality (95% CI 0.58–0.79, p<0.001). PTX3 at a cut-off level for 14.1 ng/ml (optimal cut-off value for severe sepsis) showed 63% sensitivity and 80% specificity. At a cut-off level 7.7 ng/ml (optimal cut-off value for case fatality) showed 70% sensitivity and 63% specificity in predicting case fatality on day 28.In multivariate models, high PTX3 remained an independent predictor of severe sepsis and case fatality after adjusting for potential confounders.ConclusionsA high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection.

Severe Acinetobacter baumannii Sepsis Is Associated with Elevation of Pentraxin 3

“…However, data presented here suggest that this may not be the case, but rather, elevated PTX3 production induced by select A. baumannii strains appears to correspond with increased susceptibility of mice to infection. Furthermore, in agreement with previously published patient case study data, prolonged elevation of PTX3 levels was associated with development of hypercoagulopathy and DIC in challenged animals (29)(30)(31)(32)(33)(34)(35).…”

“…3A). Thus, significant elevation in PTX3 production appeared to be associated with increased disease severity, consistent with published case studies (29)(30)(31)(32)(33)(34)(35).…”

“…Additionally, PTX3 has been shown to opsonize pathogens, thus enhancing complement activation and phagocytosis during bacterial and fungal infections, aiding in pathogen clearance through recruitment of C1q and stimulation of the Fc␥ receptor, respectively (16,(18)(19)(20)(23)(24)(25)(26)(27)(28). Despite immunoprotective properties, prolonged elevation of patient PTX3 levels has been reported to correlate with increased morbidity and mortality in severe sepsis (29)(30)(31)(32)(33)(34)(35) thought to arise from increased tissue factor (TF) expression on the surface of monocytic phagocytes and vascular endothelial cells observed in vitro following LPS stimulation (36,37). Although neutrophils store PTX3 in a preformed active state within cytoplasmic granules, giving rise to short-lived spikes in serum PTX3 levels following degranulation, prolonged elevation can arise from induced expression by monocytic cells, e.g., monocytes, macrophages, dendritic cells, and endothelial cells (17,19,25,28,38,39).…”

IL-6 trans-signaling increases expression of airways disease genes in airway smooth muscle

“…Pentraxin 3 levels also become elevated in subjects with ARDS within 24 h of diagnosis, presumably as an activator of the local innate immune system in the lung (3). In addition, elevated levels of serum pentraxin 3 have been detected in subjects with sepsis and appear to be an important biomarker of sepsis severity (69). Given the strong association of the IL-6 pathway with these conditions, our data suggest that IL-6 trans-signaling could play an important role in elevating these markers of lung disease.…”

Pentraxin-3 serum levels are associated with disease severity and mortality in patients with systemic inflammatory response syndrome

“…Recent studies have shown that PTX3 can be used as a marker for disease severity and fatal outcome in cardiovascular, inflammatory and infectious diseases [16][17][18][19][20][21]. Thus, we developed a novel assay for measurement of PTX3 in body fluids and examined the serum levels from patients with SIRS and sepsis admitted to an ICU as well as controls in order to review the validity of PTX3 as a biomarker in ICU patients.…”