ULiège, CHU
" We are facing a COVID-19 infection pandemic. This pathogenic virus is a source of pulmonary complications greatly aggravating the prognosis of our patients. Today, both the pathophysiological mechanisms involved and the predictive markers of the severity of the disease remain unclear. It therefore seems urgent to be able to identify prognostic and diagnostic markers for our patients on the one hand. In this context, several paths that can quickly be explored appear to us to be critical. This is why we are planning the evaluation of the neutrophilic activation pathway by studying the Exosomes and circulating nucleosomes containing neutrophilic activation markers. This tool would make it possible to identify people at risk of clinical deterioration but also to approach the pathophysiological mechanisms involved. "
Funding: Fonds Léon Fredericq
Publication References: 1Danthi P. Viruses and the Diversity of Cell death Annu. Rev. Virol. (2016) 3:533–53 2 Wang Y et al. Histone hypercitrullination mediates chromatin decondensation and neutrophil extracellular trap formation. J. Cell Biol. (2009) 184(2):205–213 3 Kalaaji M. Glomerular apoptotic nucleosomes are central target structures for nephritogenic antibodies in human SLE nephritis (2007) 71(7):665-672 4 Ashar H et al. The Role of Extracellular Histones in Influenza Virus Pathogenesis (2018) Jan;188(1):135-148 5 Marcos V. et al. CXCR2 mediates NADPH oxidase-independent neutrophil extracellular trap formation in cystic fibrosis airway inflammation. Nat Med (2010) 16:1018–23 6 Hoeksema M. et al. Histones as mediators of host defense, inflammation and thrombosis. Future Microbiol (2016) 11:441–53. 7 Zeerlander S. Elevated nucleosome levels in systemic inflammation and sepsis. Critical Care Medicine (2003) 31(7):1947-51 8 Letendre JA. Determining prognosis in canine sepsis by bedside measurement of cell-free DNA and nucleosomes. J Vet Emerg Crit Care (San Antonio). (2018) Nov;28(6):503-511 9 Letendre JA. Concentrations of Plasma Nucleosomes but Not Cell-Free DNA Are Prognostic in Dogs Following Trauma. Frontiers in Veterinary Science. (2018) Jul;5: 180 10 Geiger S. Nucleosomes as a new prognostic marker in early cerebral stroke. J Neurol (2007) 254:617–623 11 Borissoff JI. Elevated Levels of Circulating DNA and Chromatin Are Independently Associated With Severe Coronary Atherosclerosis and a Prothrombotic State. Arterioscler Thromb Vasc Biol. (2013) 33:2032 2040 12 Holdenrieder S. et al. Nucleosomes in serum as a marker for cell death. Clin Chem Lab Med. 2001 Jul;39(7):596-605 13 Papayannopoulos, V. Neutrophil extracellular traps in immunity and disease. Nat Rev Immunol 2018 18:134–147 Guiot, J., Struman, I., Louis, E., Louis, R., Malaise, M., Njock MS. Exosomal miRNAs in Lung Diseases: From Biologic Function to Therapeutic Targets. J Clin Med. 2019 Aug 29;8(9) Guiot*, J., Makon-Sébastien*, N., Henket, M., Nivelles, O., Thiry, M., Dequiedt, F., Corhay, J.-L., Louis, R., & Struman, I. Sputum exosomal microRNAs as promising biomarkers for Idiopathic Pulmonary Fibrosis. Thorax 2018 Sep 22 - Guiot, J., Struman, I., Chavez, V., Henket, M., Herzog, M., Scoubeau, K., Hardat, N., Bondue, B., Corhay, J.-L., Moermans, C., & Louis, R. (2017, Augustus). Altered epigenetic features in circulating nucleosomes in idiopathic pulmonary fibrosis. Clinical Epigenetics, 9:84.
Contact: J.Guiot@chuliege.be