New Approaches to Identify Sepsis Biomarkers: The Importance of Model and Sample Source for Mass Spectrometry.

Angélique Blangy-Letheule,Bertrand Rozec,Benjamin Lauzier,Michel De Waard,Antoine Persello,Luc Demaison

doi:10.1155/2020/6681073

Abstract

Septic shock is a systemic inflammatory response syndrome associated with circulatory failure leading to organ failure with a 40% mortality rate. Early diagnosis and prognosis of septic shock are necessary for specific and timely treatment. However, no predictive biomarker is available. In recent years, improvements in proteomics-based mass spectrometry have improved the detection of such biomarkers. This approach can be performed on different samples such as tissue or biological fluids. Working directly from human samples is complicated owing to interindividual variability. Indeed, patients are admitted at different stages of disease development and with signs of varying severity from one patient to another. All of these elements interfere with the identification of early, sensitive, and specific septic shock biomarkers. For these reasons, animal models of sepsis, although imperfect, are used to control the kinetics of the development of the pathology and to standardise experimentation, facilitating the identification of potential biomarkers. These elements underline the importance of the choice of animal model used and the sample to be studied during preclinical studies. The aim of this review is to discuss the relevance of different approaches to enable the identification of biomarkers that could indirectly be relevant to the clinical setting.

Highlights

Sepsis and septic shock are common causes for admission to intensive care units
Over the last 50 years, studies have demonstrated that myocardial dysfunction is a common finding in septic patients and approximately 50% of septic patients present signs of myocardial decompensation with variable development kinetics depending on the patient resulting in excess mortality of more than 60% [3]
Septic shock is a complex and multifactorial pathology presenting a great heterogeneity of clinical manifestations

Summary

Introduction

Sepsis and septic shock are common causes for admission to intensive care units. Sepsis is defined as organ dysfunction resulting from a deregulated host response to infection [1]. Septic shock is the most severe manifestation of sepsis It is characterized by persistent hypotension, associated with metabolic dysfunction and significant tissue suffering. Septic shock is a complex and multifactorial pathology presenting a great heterogeneity of clinical manifestations. This explains the differences in the kinetics of organ dysfunction and complicates its early diagnosis and appropriate management. The use of early biomarkers and therapeutic targets that are sensitive and specific to the evolution of the pathology would facilitate rapid diagnosis and early management of patients, limiting organ dysfunctions, cardiac dysfunction, and optimizing patient chances of survival. Proteomics based on mass spectrometry (MS) enable the use of different samples such as biological tissues or fluids based on patient cohorts or animal models in order to identify biomarkers and/or therapeutic targets. This review seeks to discuss the quality and properties of different models that will enable the potential identification of clinically relevant biomarkers

Mass Spectrometry for the Identification of Sepsis Biomarkers

Animal Models

Nonsurgical Models

Findings

Conflicts of Interest