Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality
J Bauzá-Martinez, F Aletti, B B Pinto, V Ribas, M A Odena, R Díaz, E Romay, R Ferrer, E B Kistler, G Tedeschi, G W Schmid-Schönbein, A Herpain, K Bendjelid, E de Oliveira, J Bauzá-Martinez, F Aletti, B B Pinto, V Ribas, M A Odena, R Díaz, E Romay, R Ferrer, E B Kistler, G Tedeschi, G W Schmid-Schönbein, A Herpain, K Bendjelid, E de Oliveira
Abstract
Background: Uncontrolled proteolysis contributes to cell injury and organ dysfunction in animal models of circulatory shock. We investigated in humans the relationship between septic shock, proteolysis, and outcome.
Methods: Intensive care patients with septic shock (n=29) or sepsis (n=6) and non-hospitalised subjects (n=9) were recruited as part of the prospective observational trial 'ShockOmics' (ClinicalTrials.gov Identifier NCT02141607). A mass spectrometry-based approach was used to analyse the plasma peptidomes and the origin of circulating peptides from proteolysis in the enrolled subjects.
Results: Evidence of systemic proteolysis was indicated by a larger number of circulating peptides in septic shock patients, compared with septic patients and non-hospitalised healthy subjects. The peptide count and abundance in the septic shock patients were greater in patients who died (n=6) than in survivors (n=23), suggesting an association between magnitude of proteolysis and outcome. In silico analysis of the peptide sequences and of the sites of cleavage on the proteins of origin indicated a predominant role for serine proteases, such as chymotrypsin, and matrix metalloproteases in causing the observed proteolytic degradation.
Conclusions: Systemic proteolysis is a novel fundamental pathological mechanism in septic shock. Plasma peptidomics is proposed as a new tool to monitor clinical trajectory in septic shock patients.
Clinical trial registration: NCT02141607.
Keywords: in-hospital mortality; mass spectrometry; peptidomics; proteolysis; septic shock.
Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.
Source: PubMed