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Project

Study of the contribution of microRNAs as specific biomarkers and key players of immune alteration in pediatric sepsis

Project supervisor

Labo of hospitaal waar het project plaatsvindt

Laboratory or Hospital where the main work will be performed : HUDERF/ laboratory of pediatric, inflammation unit

Objectives of research

• To define miRNA biomarker(s) for sepsis, for stratification of the disease severity and for prediction of patients’ prognosis during therapy
• To evaluate of the impact of deregulated miRNAs on the inflammatory process in sepsis
• To assess the contribution of miRNA-derived monocytes to the immune alteration usually found in sepsis

Summary

Sepsis is a life-threatening disease that manifests by dramatic dysregulation of host response to infection and multiple organ failure. it is considered by the WHO as a global health priority giving the high morbidity and mortality it causes worldwide despite progress in intensive care treatment. Timely diagnosis of sepsis is critical for the appropriate monitoring and treatment of the patients. Clinical and biological inflammatory parameters are being used for the diagnosis and the evaluation of the disease progress; however, such classical markers lack specificity. On the other hand, body of evidence has shown the occurrence of severe immunosuppression in sepsis after initial excessive inflammation. This includes phenotypic and functional alteration of blood leucocyte cells such as monocytes. The molecular explanation of this immune alteration in not fully understood. As a result, patients fail to clear ongoing infection and display increased susceptibility to secondary infections. We propose here a multicenter prospective study that invloves 3 European hospitals including HUDERF[1]ULB. Given the importance of micro-RNAs (miRNAs) - small non-protein coding RNA molecules - in the regulation of many biological processes, including in immunity and inflammation, we ask whether the detection of their level in the blood could be useful as specific biomarker for sepsis and to what extent this could help stratify disease severity. We will perform systematic study to define specific miRNA marker(s) and to evaluate their relationship with inflammatory states. We also plan to determine their cellular source and their potent role in the immune alteration usually found in sepsis by investigating the contribution of monocytes, one of the major leucocyte cells of the immune system. We believe this study will allow identification of novel biomarkers for sepsis and for prediction of patients’ prognosis during therapy. The investigation will also help us better understand sepsis pathogenesis.