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.

The long pentraxin PTX3: A prototypical sensor of tissue injury and a regulator of homeostasis

“…185 Similarly, in a Danish study on 261 patients admitted to intensive care unit for SIRS, higher expression of PTX3 correlates with sepsis and septic shock. 186 In the absence of infection, a "sepsis-like" syndrome is observed after cardiopulmonary resuscitation. In conditions of total body ischemia and reperfusion, the systemic inflammatory response is characterized by the presence of endotoxin in plasma, deregulation of cytokine production and coagulation defects.…”

Inflammatory biomarkers and cancer: CRP and suPAR as markers of incident cancer in patients with serious nonspecific symptoms and signs of cancer

“…Plasma concentrations of ficolin-1, ficolin-2, ficolin-3, pentraxin-3 and MBL were determined by sandwich ELISAs using specific in house-produced monoclonal antibodies as previously described. [29][30][31][32][33] All assays were optimized for automated analysis in 384-well format on Biomek FX (Beckman Coulter, Fullerton, CA).…”

Pentraxins in the activation and regulation of innate immunity

“…Higher PTX3 levels correlated with SAPS2 score and patients with high PTX3 levels at admission have higher 90-day mortality than patients with lower levels. 156 In addition, a study on more than 500 patients demonstrates that a high PTX3 level on hospital admission predicts severe sepsis and case fatality in patients with suspected infection. 157 In 132 adult patients admitted to ICU with positive blood culture for the most common causative organisms in community-acquired bacteremia (Staphylococcus aureus, Streptococcus pneumoniae, b-hemolytic streptococci, or E. coli), maximum PTX3 values on days 1-4 were observed in non-survivors, while in this cohort CRP levels were not predictive of mortality.…”