Inflammatory and epigenetic markers of prognosis of patients with sepsis after hospital discharge

• Grant number: 17/13715-9
• Support Opportunities: Regular Research Grants
• Start date: June 01, 2018
• End date: May 31, 2020
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Marcel Cerqueira Cesar Machado
• Grantee: Marcel Cerqueira Cesar Machado
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated researchers: Antonio Carlos Nogueira ; Francisco Garcia Soriano ; Rodrigo Cerqueira Borges ; Rui Curi

Abstract

Post-septic patients, after hospital discharge, present high mortality rate, reaching 30% after one year, 70% after two years, and 81.9% after five years. High incidence of causes of post-septic patient death and prognostic markers, after hospital discharge, remain unknown and require investigation. There is a close relationship between plasma levels of C-reactive protein (CRP) - and therefore the inflammatory state - and mortality after hospital discharge in post-septic patients. Macrophages are one of the main effector cells of innate immunity. These cells exhibit receptors that bind to pathogen-associated molecular patterns (PAMPs) and/or damage-associated molecular patterns (DAMPS), which trigger the inflammatory response. After PAMP or DAMP binding, there is activation of inflammatory pathways, and of the NLRP3 inflammasome. In patients with sepsis, exacerbated activation of these mechanisms impairs acute inflammatory resolution, leading to systemic inflammation state. MicroRNAs (miRNAs) are non-coding and small RNAs that act as post-transcriptional regulators of gene expression. Alterated expressions of these molecules have been associated with various diseases. MiRNAs have been suggested to be potential prognostic biomarkers in septic patients. Patients exhibit modified expression of the following miRNAs in the acute phase of sepsis: miR-15a, -16, -122, -193 and -483-5p, -297, -574-5p, -34a, -27a, -130a, -155, -150, -146a, -223 and -499-5p. Little is known however about the miRNA profile after hospital discharge in post-septic patients. The aim of this study is to identify inflammatory and epigenetic markers of prognosis of post-septic patients after hospital discharge. Plasma concentrations of cytokines (pro- and anti-inflammatory), exossomal miRNA profile, and monocyte activation state will be evaluated in patients that presented severe sepsis after hospital discharge. These patients will be evaluated at different periods: during the septic period, at the time of hospital discharge and 3, 6, and 12 months afterwards. Predictive plasma markers of septic patients with survival prognosis after hospital discharge will be established, contributing to a more accurate treatment and reduced mortality rate. (AU)