An early increase in endothelial protein C receptor is associated with excess mortality in pneumococcal pneumonia with septic shock in the ICU

Agnès Chapelet 1, 2, 3 Yohann Foucher 4 Nathalie Gérard 5 Christophe Rousseau 6 Olivier Zambon 2 Cédric Bretonnière 2 Jean-Paul Mira 6, 7 Béatrice Charreau 3, 5 Christophe Guitton 1, 2, 8, *
* Corresponding author
1 U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
2 Service de soins intensifs [CHU Nantes]
3 ITUN - Institut de transplantation urologie-néphrologie
4 SPHERE - MethodS in Patients-centered outcomes and HEalth ResEarch
5 Team 4 - U1064 Inserm - CRTI - Immunoregulation And Immunointervention in Transplantation and Autoimmunity
U1064 Inserm - CRTI - Centre de Recherche en Transplantation et Immunologie
6 IC UM3 (UMR 8104 / U1016) - Institut Cochin
7 Unité de Soins Intensifs [CHU Cochin]
8 Service de soins intensifs [CH Le Mans]
Abstract : Background: This study investigated changes in plasma level of soluble endothelial protein C receptor (sEPCR) in association with outcome in patients with septic shock. We explored sEPCR for early sepsis prognosis assessment and constructed a scoring system based on clinical and biological data, in order to discriminate between surviving at hospital discharge and non-surviving patients. Methods: Clinical data and samples were extracted from the prospective “STREPTOGENE” cohort. We enrolled 278 patients, from 50 intensive care units (ICUs), with septic shock caused by pneumococcal pneumonia. Patients were divided into survivors (n =194) and non-survivors (n =84) based on in-hospital mortality. Soluble EPCR plasma levels were quantified at day 1 (D1) and day 2 (D2) by ELISA. The EPCR gene A3 haplotype was determined. Patients were followed up until hospital discharge. Univariate and multivariate analyses were performed. A scoring system was constructed using least absolute shrinkage and selection operator (lasso) logistic regression for selecting predictive variables. Results: In-hospital mortality was 30.2% (n =84). Plasma sEPCR level was significantly higher at D1 and D2 in nonsurviving patients compared to patients surviving to hospital discharge (p =0.0447 and 0.0047, respectively). Early increase in sEPCR at D2 was found in non-survivors while a decrease was observed in the survival group (p =0.0268). EPCR A3 polymorphism was not associated with mortality. Baseline sEPCR level and its variation from D1 to D2 were independent predictors of in-hospital mortality. The scoring system including sEPCR predicted mortality with an AUC of 0.75. Conclusions: Our findings confirm that high plasma sEPCR and its increase at D2 are associated with poor outcome in sepsis and thus we propose sEPCR as a key player in the pathogenesis of sepsis and as a potential biomarker of sepsis outcome.
Keywords : Sepsis Soluble EPCR In-hospital mortality Predictive score Early biomarker Sepsis outcome Pneumococcal pneumonia
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Agnès Chapelet, Yohann Foucher, Nathalie Gérard, Christophe Rousseau, Olivier Zambon, et al.. An early increase in endothelial protein C receptor is associated with excess mortality in pneumococcal pneumonia with septic shock in the ICU. Critical Care, BioMed Central, 2018, 22 (1), ⟨10.1186/s13054-018-2179-6⟩. ⟨inserm-02157511⟩

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