Dysregulated activities of proline-specific enzymes in septic shock patients (sepsis-2).

Gwendolyn Vliegen,Bart ‘S Jongers,Esther Peters,Kaat Kehoe,Emilie De Hert,An Bracke,Samir Kumar-Singh,Robert Verkerk,Erik Fransen,Anne-Marie Lambeir,Peter Pickkers,Ingrid De Meester,Philippe G Jorens

doi:10.1371/journal.pone.0231555

Abstract

The proline-specific enzymes dipeptidyl peptidase 4 (DPP4), prolylcarboxypeptidase (PRCP), fibroblast activation protein α (FAP) and prolyl oligopeptidase (PREP) are known for their involvement in the immune system and blood pressure regulation. Only very limited information is currently available on their enzymatic activity and possible involvement in patients with sepsis and septic-shock. The activity of the enzymes was measured in EDTA-plasma of patients admitted to the intensive care unit (ICU): 40 septic shock patients (sepsis-2) and 22 ICU control patients after major intracranial surgery. These data were used to generate receiver operating characteristic (ROC) curves. A survival analysis (at 90 days) and an association study with other parameters was performed. PRCP (day 1) and PREP (all days) enzymatic activities were higher in septic shock patients compared to controls. In contrast, FAP and DPP4 were lower in these patients on all studied time points. Since large differences were found, ROC curves were generated and these yielded area under the curve (AUC) values for PREP, FAP and DPP4 of 0.88 (CI: 0.80-0.96), 0.94 (CI: 0.89-0.99) and 0.86 (CI: 0.77-0.95), respectively. PRCP had a lower predicting value with an AUC of 0.71 (CI: 0.58-0.83). A nominally significant association was observed between survival and the DPP4 enzymatic activity at day 1 (p<0.05), with a higher DPP4 activity being associated with an increase in survival. All four enzymes were dysregulated in septic shock patients. DPP4, FAP and PREP are good in discriminating between septic shock patients and ICU controls and should be further explored to see whether they are already dysregulated in earlier stages, opening perspectives for their further investigation as biomarkers in sepsis. DPP4 also shows potential as a prognostic biomarker. Additionally, the associations found warrant further research.

Highlights

Sepsis remains a major problem in the intensive care unit (ICU), where approximately one third of admitted patients is diagnosed with sepsis [1]
Sepsis is currently defined as a lifethreatening organ dysfunction caused by a dysregulated host response to infection and septic shock is defined as a subset of sepsis in which profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone [2]
We studied the enzymatic activities of dipeptidyl peptidase 4 (DPP4), PRCP, fibroblast activation protein α (FAP) and prolyl oligopeptidase (PREP) in the plasma of patients with septic shock, since they are known for their involvement in the immune system and blood pressure regulation, important factors playing a key role in sepsis, as will be discussed below

Summary

Introduction

Sepsis remains a major problem in the intensive care unit (ICU), where approximately one third of admitted patients is diagnosed with sepsis [1]. We studied the enzymatic activities of DPP4, PRCP, FAP and PREP in the plasma of patients with septic shock (sepsis-2), since they are known for their involvement in the immune system and blood pressure regulation, important factors playing a key role in sepsis, as will be discussed below. They are measured in plasma or serum with specific assays. It is conceivable that they could be involved in pathogenesis of sepsis and septic shock, as will be outlined below

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Discussion

Conclusion