Cargando…
Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach
BACKGROUND: As early and appropriate care of severe septic patients is associated with better outcome, understanding of the very first events in the disease process is needed. Pan-genomic analyses offer an interesting opportunity to study global genomic response within the very first hours after sep...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer International Publishing
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512996/ https://www.ncbi.nlm.nih.gov/pubmed/26215705 http://dx.doi.org/10.1186/s40635-014-0020-3 |
_version_ | 1782382570877485056 |
---|---|
author | Cazalis, Marie-Angélique Lepape, Alain Venet, Fabienne Frager, Florence Mougin, Bruno Vallin, Hélène Paye, Malick Pachot, Alexandre Monneret, Guillaume |
author_facet | Cazalis, Marie-Angélique Lepape, Alain Venet, Fabienne Frager, Florence Mougin, Bruno Vallin, Hélène Paye, Malick Pachot, Alexandre Monneret, Guillaume |
author_sort | Cazalis, Marie-Angélique |
collection | PubMed |
description | BACKGROUND: As early and appropriate care of severe septic patients is associated with better outcome, understanding of the very first events in the disease process is needed. Pan-genomic analyses offer an interesting opportunity to study global genomic response within the very first hours after sepsis. The objective of this study was to investigate the systemic genomic response in severe intensive care unit (ICU) patients and determine whether patterns of gene expression could be associated with clinical severity evaluated by the severity score. METHODS: Twenty-eight ICU patients were enrolled at the onset of septic shock. Blood samples were collected within 30 min and 24 and 48 h after shock and genomic response was evaluated using microarrays. The genome-wide expression pattern of blood leukocytes was sequentially compared to healthy volunteers and after stratification based on Simplified Acute Physiology Score II (SAPSII) score to identify potential mechanisms of dysregulation. RESULTS: Septic shock induces a global reprogramming of the whole leukocyte transcriptome affecting multiple functions and pathways (>71% of the whole genome was modified). Most altered pathways were not significantly different between SAPSII-high and SAPSII-low groups of patients. However, the magnitude and the duration of these alterations were different between these two groups. Importantly, we observed that the more severe patients did not exhibit the strongest modulation. This indicates that some regulation mechanisms leading to recovery seem to take place at the early stage. CONCLUSIONS: In conclusion, both pro- and anti-inflammatory processes, measured at the transcriptomic level, are induced within the very first hours after septic shock. Interestingly, the more severe patients did not exhibit the strongest modulation. This highlights that not only the responses mechanisms by themselves but mainly their early and appropriate regulation are crucial for patient recovery. This reinforces the idea that an immediate and tailored aggressive care of patients, aimed at restoring an appropriately regulated immune response, may have a beneficial impact on the outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40635-014-0020-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4512996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer International Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-45129962015-07-27 Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach Cazalis, Marie-Angélique Lepape, Alain Venet, Fabienne Frager, Florence Mougin, Bruno Vallin, Hélène Paye, Malick Pachot, Alexandre Monneret, Guillaume Intensive Care Med Exp Research BACKGROUND: As early and appropriate care of severe septic patients is associated with better outcome, understanding of the very first events in the disease process is needed. Pan-genomic analyses offer an interesting opportunity to study global genomic response within the very first hours after sepsis. The objective of this study was to investigate the systemic genomic response in severe intensive care unit (ICU) patients and determine whether patterns of gene expression could be associated with clinical severity evaluated by the severity score. METHODS: Twenty-eight ICU patients were enrolled at the onset of septic shock. Blood samples were collected within 30 min and 24 and 48 h after shock and genomic response was evaluated using microarrays. The genome-wide expression pattern of blood leukocytes was sequentially compared to healthy volunteers and after stratification based on Simplified Acute Physiology Score II (SAPSII) score to identify potential mechanisms of dysregulation. RESULTS: Septic shock induces a global reprogramming of the whole leukocyte transcriptome affecting multiple functions and pathways (>71% of the whole genome was modified). Most altered pathways were not significantly different between SAPSII-high and SAPSII-low groups of patients. However, the magnitude and the duration of these alterations were different between these two groups. Importantly, we observed that the more severe patients did not exhibit the strongest modulation. This indicates that some regulation mechanisms leading to recovery seem to take place at the early stage. CONCLUSIONS: In conclusion, both pro- and anti-inflammatory processes, measured at the transcriptomic level, are induced within the very first hours after septic shock. Interestingly, the more severe patients did not exhibit the strongest modulation. This highlights that not only the responses mechanisms by themselves but mainly their early and appropriate regulation are crucial for patient recovery. This reinforces the idea that an immediate and tailored aggressive care of patients, aimed at restoring an appropriately regulated immune response, may have a beneficial impact on the outcome. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40635-014-0020-3) contains supplementary material, which is available to authorized users. Springer International Publishing 2014-08-20 /pmc/articles/PMC4512996/ /pubmed/26215705 http://dx.doi.org/10.1186/s40635-014-0020-3 Text en © Cazalis et al.; licensee Springer 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. |
spellingShingle | Research Cazalis, Marie-Angélique Lepape, Alain Venet, Fabienne Frager, Florence Mougin, Bruno Vallin, Hélène Paye, Malick Pachot, Alexandre Monneret, Guillaume Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach |
title | Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach |
title_full | Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach |
title_fullStr | Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach |
title_full_unstemmed | Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach |
title_short | Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach |
title_sort | early and dynamic changes in gene expression in septic shock patients: a genome-wide approach |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512996/ https://www.ncbi.nlm.nih.gov/pubmed/26215705 http://dx.doi.org/10.1186/s40635-014-0020-3 |
work_keys_str_mv | AT cazalismarieangelique earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT lepapealain earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT venetfabienne earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT fragerflorence earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT mouginbruno earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT vallinhelene earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT payemalick earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT pachotalexandre earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach AT monneretguillaume earlyanddynamicchangesingeneexpressioninsepticshockpatientsagenomewideapproach |