Amsterdam UMC, University of Amsterdam, Center for Experimental Molecular Medicine, Amsterdam Infection & Immunity, Amsterdam, Netherlands; Amsterdam UMC, University of Amsterdam, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam, Netherlands
Amsterdam UMC, University of Amsterdam, Center for Experimental Molecular Medicine, Amsterdam Infection & Immunity, Amsterdam, Netherlands
Lonneke A van Vught
Amsterdam UMC, University of Amsterdam, Center for Experimental Molecular Medicine, Amsterdam Infection & Immunity, Amsterdam, Netherlands
Maryse A Wiewel
Amsterdam UMC, University of Amsterdam, Center for Experimental Molecular Medicine, Amsterdam Infection & Immunity, Amsterdam, Netherlands
Arie J Hoogendijk
Amsterdam UMC, University of Amsterdam, Center for Experimental Molecular Medicine, Amsterdam Infection & Immunity, Amsterdam, Netherlands
Ingelore Baessman
Cologne Center for Genomics, University of Cologne, Cologne, Germany
Marek Franitza
Cologne Center for Genomics, University of Cologne, Cologne, Germany
Peter Nürnberg
Cologne Center for Genomics, University of Cologne, Cologne, Germany; Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany
Janneke Horn
Amsterdam UMC, University of Amsterdam, Department of Intensive Care Medicine, Amsterdam, Netherlands
Olaf L Cremer
Department of Intensive Care, University Medical Center Utrecht, Utrecht, Netherlands
Marc J Bonten
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands
Marcus J Schultz
Amsterdam UMC, University of Amsterdam, Department of Intensive Care Medicine, Amsterdam, Netherlands
Tom van der Poll
Amsterdam UMC, University of Amsterdam, Center for Experimental Molecular Medicine, Amsterdam Infection & Immunity, Amsterdam, Netherlands; Amsterdam UMC, University of Amsterdam, Division of Infectious Diseases, Amsterdam, Netherlands
Molecular Diagnosis and Risk Stratification in Sepsis (MARS) consortium
The extent of non-coding RNA alterations in patients with sepsis and their relationship to clinical characteristics, soluble mediators of the host response to infection, as well as an advocated in vivo model of acute systemic inflammation is unknown. Here we obtained whole blood from 156 patients with sepsis and 82 healthy subjects among whom eight were challenged with lipopolysaccharide in a clinically controlled setting (human endotoxemia). Via next-generation microarray analysis of leukocyte RNA we found that long non-coding RNA and, to a lesser extent, small non-coding RNA were significantly altered in sepsis relative to health. Long non-coding RNA expression, but not small non-coding RNA, was largely recapitulated in human endotoxemia. Integrating RNA profiles and plasma protein levels revealed known as well as previously unobserved pathways, including non-sensory olfactory receptor activity. We provide a benchmark dissection of the blood leukocyte ‘regulome’ that can facilitate prioritization of future functional studies.
