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.
Highlights
Pentraxins are a superfamily of pattern recognition molecules belonging to the humoral arm of the innate immunity
A number of samples, from both patients (n = 38) and controls (n = 31), exceeded the cut-off point on the control plates, as described previously. These samples were re-run in a sampling buffer with addition of CrossDown buffer and EDTA in attempt to remove the interfering antibodies disturbing the signal from the PTX3 detection
All samples were applied in duplicates, and the mean values were used in subsequent calculations
Summary
Pentraxins are a superfamily of pattern recognition molecules belonging to the humoral arm of the innate immunity. Pentraxin-3 (PTX3) is the prototypic long pentraxin whereas the classical acute-phase protein, C-reactive protein (CRP), and serum amyloid P component (SAP), belong to the short pentraxins. This division is based on the length of their primary structure. Besides from a signal peptide, the primary transcript of PTX3 consists of a classical pentraxin like C-terminal domain containing the pentraxin signature (HxCxS/TWxS, where x is any amino acid) and a unique N-terminal domain [1]. PTX3 adopts to a complex multimeric formation creating an octamer composed of two covalently linked tetramers. PTX3 contains a single N-glycosylation site at Asn220 in the C-terminal domain that is fully occupied by complex type oligosaccharides. The glycosylation state has been shown to affect the binding to different ligands and suggested to influence the biological activity [2]
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