Proteolysis in septic shock patients: plasma peptidomic patterns are associated with mortality. (November 2018)

• Record Type: Journal Article
• Authors: Bauzá-Martinez, J.; Aletti, F.; Pinto, B.B.; Ribas, V.; Odena, M.A.; Díaz, R.; Romay, E.; Ferrer, R.; Kistler, E.B.; Tedeschi, G.; Schmid-Schönbein, G.W.; Herpain, A.; Bendjelid, K.; de Oliveira, E.
• Is Part Of: British journal of anaesthesia. Volume 121:Number 5(2018)
• Page Start: 1065
• Page End: 1074
• Publication Date: 2018-11
• Subjects: in-hospital mortality -- mass spectrometry -- peptidomics -- proteolysis -- septic shock; Anesthesiology -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1016/j.bja.2018.05.072
• Languages: English
• ISSNs: 0007-0912

Abstract

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 .