Early and dynamic changes in gene expression in septic shock patients: a genome-wide approach

Abstract

BackgroundAs 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.MethodsTwenty-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.ResultsSeptic 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.ConclusionsIn 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 materialThe online version of this article (doi:10.1186/s40635-014-0020-3) contains supplementary material, which is available to authorized users.

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

“…28 septic shock patients and 25 HV admitted into 2 ICUs of HCL were included in this study to explore the early transcriptome modulation after septic shock. Inclusion / exclusion criteria, clinical description and ethical considerations of the cohort have been previously published elsewhere (Cazalis et al 2014). The first blood sample was collected at the onset of shock (i.e., within 30 min after the beginning of vasoactive treatment, D0) and at day 1 (D1) and day 2 (D2) after shock.…”

Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia

“…To date, time series analyzing changes in gene expression have been focused on animal models of sepsis (34), the endotoxin response in healthy volunteers (35), the response to trauma and subsequent infection (26), and early events in sepsis (29), and authors of a recent analysis of timematched cohorts defined a gene set distinguishing sterile inflammation from infectious inflammation (12). In general, clearer resolution of temporal differences is critical to resolving heterogeneity in observed sepsis responses within and between patients.…”

“…Interpretation of gene expression patterns in sepsis may be complicated by dynamic differences in the host response over time (10,29). We explored temporal changes in gene expression for patients with FP and patients with CAP from whom serial samples following ICU admission were available.…”

Correlations between ACE single nucleotide polymorphisms and prognosis of patients with septic shock

“…Although great improvements have been achieved, SS continues to be the leading cause of mortality in ICU all over the globe [43]. The increased protein expression of AngII type 1 receptor was associated with increased 28-day mortality in SS as well as decreased blood pressure [44].…”