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The circulatory small non-coding RNA landscape in community-acquired pneumonia on intensive care unit admission |
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| Authors: | Hina N. Khan Aldo Jongejan Lonneke A. van Vught Janneke Horn Marcus J. Schultz Aeilko H. Zwinderman Olaf L. Cremer Marc J. Bonten Tom van der Poll Brendon P. Scicluna |
| Affiliation: | 1. Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands Contribution: Data curation (equal), Formal analysis (equal), Writing - original draft (equal), Writing - review & editing (equal);2. Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands Contribution: Formal analysis (equal), Writing - review & editing (equal);3. Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands Contribution: Data curation (equal), Writing - review & editing (equal);4. Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands Contribution: Data curation (equal), Writing - review & editing (equal);5. Department of Intensive Care & Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Amsterdam University Medical Centers, location Academic Medical Center, Amsterdam, The Netherlands Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand Contribution: Data curation (equal), Writing - review & editing (equal);6. Department of Intensive Care, University Medical Center Utrecht, Utrecht, The Netherlands Contribution: Writing - review & editing (equal);7. Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands Contribution: Writing - review & editing (equal);8. Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands Division of Infectious Diseases, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Contribution: Conceptualization (equal), Funding acquisition (equal), Writing - review & editing (equal);9. Center for Experimental Molecular Medicine, Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, The Netherlands |
| Abstract: | Community-acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non-coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP-associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non-infectious control participants. Plasma small RNA-sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over-represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to Streptococcus pneumoniae infection. Pathway analysis of plasma miRNA signatures unique to Influenza or Streptococcus pneumoniae infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways. |
| Keywords: | community-acquired pneumonia micro RNA Sepsis small non-coding RNA Streptococcus pneumoniae |