Abstract

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 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, were 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.

Data availability

The datasets generated and analyzed in the current study are available in the Gene Expression Omnibus of the National Center for Biotechnology Information repository with primary data accession numbers GSE134364 (super-series), GSE134347 for patients and healthy volunteers (HTA 2.0 microarray), GSE134356 for the human endotoxemia model samples (HTA 2.0 microarray) and GSE134358 for all patients, healthy volunteers and human endotoxemia samples (miRNA-4.1 microarray).

Article and author information

Author details

  1. Brendon P Scicluna

    Center for Experimental Molecular Medicine, AMC, Amsterdam, Netherlands
    For correspondence
    b.scicluna@amc.uva.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2826-0341
  2. Fabrice Uhel

    Center for Experimental Molecular Medicine, AMC, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4946-8184
  3. Lonneke A van Vught

    Center for Experimental Molecular Medicine, AMC, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Maryse A Wiewel

    Center for Experimental Molecular Medicine, AMC, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Arie J Hoogendijk

    Center for Experimental Molecular Medicine, AMC, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Ingelore Baessman

    Cologne Center for Genomics, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Marek Franitza

    Cologne Center for Genomics, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Peter Nürnberg

    Cologne Center for Genomics, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  9. Janneke Horn

    Intensive care medicine, AMC, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Olaf L Cremer

    Intensive care medicine, University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Marc J Bonten

    Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Marcus J Schultz

    Intensive care medicine, AMC, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. Tom van der Poll

    Infectious diseases, AMC, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  14. MARS consortium

Funding

Innovative Medicines Initiative (115523 | 115620 | 115737)

  • Marc J Bonten

Center for Translational Molecular Medicine (04I-201)

  • Tom van der Poll

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Evangelos J Giamarellos-Bourboulis, Attikon University Hospital, Greece

Ethics

Human subjects: The institutional review boards of both participating centers approved an opt-out consent method (IRB No. 10-056C). The Dutch Central Committee on Research Involving Human Subjects and the Medical Ethics Committee of the Academic Medical Center, Amsterdam, the Netherlands, approved the study. Written informed consent was obtained from all healthy participants.

Version history

  1. Received: May 5, 2020
  2. Accepted: December 10, 2020
  3. Accepted Manuscript published: December 11, 2020 (version 1)
  4. Version of Record published: December 31, 2020 (version 2)

Copyright

© 2020, Scicluna et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Brendon P Scicluna
  2. Fabrice Uhel
  3. Lonneke A van Vught
  4. Maryse A Wiewel
  5. Arie J Hoogendijk
  6. Ingelore Baessman
  7. Marek Franitza
  8. Peter Nürnberg
  9. Janneke Horn
  10. Olaf L Cremer
  11. Marc J Bonten
  12. Marcus J Schultz
  13. Tom van der Poll
  14. MARS consortium
(2020)
The leukocyte non-coding RNA landscape in critically ill patients with sepsis
eLife 9:e58597.
https://doi.org/10.7554/eLife.58597

Share this article

https://doi.org/10.7554/eLife.58597

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