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GSE57065
Homo sapiens
105 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: As early and appropriate care of severe septic patients is associated with better outcome, understanding of 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 severity score. Methods: Twenty-eight ICU patients were enrolled at the onset of septic shock. Blood samples were collected within 30 minutes, 24 and 48 hours 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 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 early stage. Conclusion: 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 themself 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 outcome.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality.
Publication Title
Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation.
Sample Metadata Fields
Sex, Age, Time
View Samples- Homo sapiens
- 114 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rationale: Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm on the immune system. Few studies assessed hydrocortisone impact on the transcriptional response in shock, and we are lacking data in burns. Objectives: To assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly on the immune response. Methods: We collected whole blood samples (n= 117) during a randomized controlled trial assessing the efficacy of hydrocortisone administration on burn shock. Using whole genome microarrays, we first compared burn patients from the placebo group (n=15) to healthy volunteers (n=13) to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration (n=15) or placebo (n=15) to assess hydrocortisone-induced modulation. Measurements and Main Results: Study groups were similar in terms of severity and major outcomes, but shock duration (significantly reduced in the hydrocortisone group). Many genes (n=2250) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity. Conclusions: We found that the initial host response to burn shock encompasses a wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock.
Publication Title
Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed.
Publication Title
Marked alterations of neutrophil functions during sepsis-induced immunosuppression.
Sample Metadata Fields
Disease
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