Specific elevation of DcR3 in sera of sepsis patients and its potential role as a clinically important biomarker of sepsis

Abstract

Because of its potentially important role in the pathogenesis of sepsis, the expression of soluble decoy receptor 3 (DcR3) was investigated in sera of sepsis patients. The serum levels of DcR3 and its tumor necrosis factor-like ligand TL1A and homologous decoy receptor OPG were quantified by ELISA. The values of DcR3 to diagnose sepsis were analyzed by receiver-operating characteristic (ROC) curves. The results showed that DcR3 was significantly elevated in sepsis compared to systemic inflammatory response syndrome (SIRS), a condition similar to sepsis but resulting from noninfectious insults. DcR3 showed superior area under the ROC curve (AUC, 0.958) compared to poor AUCs of TL1A and OPG. At a cut-off of 3.24 ng/mL, DcR3 predicted sepsis from SIRS with 96% sensitivity and 82.6% specificity. DcR3 also predicted sepsis from cancer and inflammatory bowel disease with equally excellent values. Therefore, DcR3 serum level has the potential to serve as a reliable biomarker of sepsis.

Fig. 1

Prominent DcR3 increases in sera of sepsis patients. DcR3 concentration was quantified by ELISA. The mean values of normal, SIRS, sepsis, RCC, and CD were 0.43 ± 0.081 (n = 46), 2.06 ± 0.33 (n = 23), 10.46 ± 1.46 (n = 25), 1.09 ± 0.24 (n = 48), and 3.23 ± 1.75 (n = 30), respectively. P value (ANOVA test) for comparison of all 5 groups was < 0.0001. Protein concentrations are shown in logarithmic scale. The bars indicate median. SIRS = Systemic inflammatory response syndrome; RCC = renal cell cancer; CD = Crohn's disease.

Fig. 2

Specific elevation of DcR3 serum level in sepsis. The concentrations of DcR3, TL1A, and OPG were quantified in sera of patients with sepsis or SIRS. Box and whiskers plots are presented to show median and interquartile (25th–75th) ranges. Protein concentrations are shown in logarithmic scale. P values (ANOVA test) for comparison among normal, sepsis, and SIRS were < 0.0001, 0.0017, and 0.5755 for DcR3, OPG, and TL1A, respectively. P values (Mann–Whitney test) between sepsis and SIRS were < 0.0001, 0.5096, 0.5214 for DcR3, OPG, and TL1A, respectively.

Fig. 3

Comparison of receiver-operating characteristic (ROC) curves for DcR3, OPG, and TL1A in predicting sepsis from SIRS. Areas under the ROC curve (AUC) for DcR3, OPG, and TL1A were 0.958 (95% confidence interval [CI]: 0.857–0.995), 0.578 (95% CI: 0.425–0.720), and 0.528 (95% CI: 0.377–0.675), respectively. P values of DcR3 versus OPG and DcR3 versus TL1A were < 0.0001, while the P value between OPG and TL1A was 0.7280.