TY - JOUR
T1 - The circulatory small non-coding RNA landscape in community-acquired pneumonia on intensive care unit admission
AU - Khan, Hina N
AU - Jongejan, Aldo
AU - van Vught, Lonneke A
AU - Horn, Janneke
AU - Schultz, Marcus J
AU - Zwinderman, Aeilko H
AU - Cremer, Olaf L
AU - Bonten, Marc J
AU - van der Poll, Tom
AU - Scicluna, Brendon P
N1 - Funding Information:
This study was funded by the Center for Translational Molecular Medicine (www.ctmm.nl; grant 04I-201). The authors thank all patients and controls volunteers who participated in this study, as well as the critical care nursing staff of the AMC ICU. The authors also acknowledge all members of the MARS consortium: Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, the Netherlands: Friso M. de Beer, Lieuwe D. J. Bos, Gerie J. Glas, Arie J. Hoogendijk, Roosmarijn T. M. van Hooijdonk, Janneke Horn, Mischa A. Huson, Laura R. A. Schouten, Marleen Straat, Luuk Wieske, Maryse A. Wiewel, Esther Witteveen. University Medical Center Utrecht, Utrecht, the Netherlands: David SY Ong, Jos F. Frencken, Maria E. Koster-Brouwer, Kirsten van de Groep, Diana M. Verboom.
Funding Information:
This study was funded by the Center for Translational Molecular Medicine ( www.ctmm.nl ; grant 04I‐201). The authors thank all patients and controls volunteers who participated in this study, as well as the critical care nursing staff of the AMC ICU. The authors also acknowledge all members of the MARS consortium: Amsterdam University Medical Centers, location Academic Medical Center, University of Amsterdam, the Netherlands: Friso M. de Beer, Lieuwe D. J. Bos, Gerie J. Glas, Arie J. Hoogendijk, Roosmarijn T. M. van Hooijdonk, Janneke Horn, Mischa A. Huson, Laura R. A. Schouten, Marleen Straat, Luuk Wieske, Maryse A. Wiewel, Esther Witteveen. University Medical Center Utrecht, Utrecht, the Netherlands: David SY Ong, Jos F. Frencken, Maria E. Koster‐Brouwer, Kirsten van de Groep, Diana M. Verboom.
Publisher Copyright:
© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - community-acquired pneumonia
KW - micro RNA
KW - Sepsis
KW - small non-coding RNA
KW - Streptococcus pneumoniae
UR - http://www.scopus.com/inward/record.url?scp=85110295103&partnerID=8YFLogxK
U2 - 10.1111/jcmm.16406
DO - 10.1111/jcmm.16406
M3 - Article
C2 - 34272809
SN - 1582-1838
VL - 25
SP - 7621
EP - 7630
JO - Journal of Cellular and Molecular Medicine
JF - Journal of Cellular and Molecular Medicine
IS - 16
ER -