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.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Western blot (left) and Commassie staining (right) of recombinant PTX3 are shown.

Lanes A and B show the culture supernatant (A) and purified protein (B) under non-reducing conditions: step ladder formation reflecting the equilibrium between the different PTX3 oligomers. Lanes C, D, E and F show the culture supernatant (C, F) and the purified protein (D, E) under reducing conditions: PTX3 monomer at 45 kDa. Lanes G and H show the purified protein (G) and the culture supernatant (H) under non-reducing conditions: the predominantly multimer of PTX3 with a MW of 340 kDa. The rightmost lane provides the standard for molecular weight ranging from 10–250 kDa.

Figure 2. Serum levels of PTX3 in healthy controls (n = 100) (left) and patients with SIRS or sepsis (n = 261) (right) are shown.

The PTX3 levels were elevated in the patients compared with the controls (Mann-Whitney, p

Figure 3. Serum levels of PTX3 in patients classified as having SIRS (n = 73), sepsis (n = 26), severe sepsis (n = 97) and septic shock (n = 65), (Kruskal-Wallis, p = 0.0001) are shown.

Ranges, interquartile ranges and medians are indicated. Using a Dunn's post test revealed that only the SIRS group differed significantly from the other groups (p0.05).

Figure 4. Kaplan-Meier plot of 90 day survival after admission to the ICU in patients with SIRS or sepsis is shown.

Closed circles indicate PTX3 levels below the 25th percentile, while open circles indicate PTX3 levels above the 25th percentile (log rank, p = 0.0004). The 25th percentile corresponds to a PTX3 level of 32.6 ng/ml.