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A genomic storm in critically injured humans

ABSTRACT: Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization.

ORGANISM(S): Homo sapiens

PROVIDER: GSE36809 | GEO | 2012/03/27

SECONDARY ACCESSION(S): PRJNA156919

REPOSITORIES: GEO

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A genomic storm in critically injured humans

Project description:Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and show that the severe stress produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected “genomic storm.” In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. Blood was sampled from 167 severe blunt trauma patients under the age of 55 yr who consented to blood sampling. The first blood sample was taken within 12 h of the injury and 1, 4, 7, 14, 21, and 28 d after injury. Study subjects were treated under the guidance of standard operating procedures developed, implemented, and audited across all participating centers to minimize treatment variation. In addition, 37 healthy control subjects were sampled. Total blood leukocytes were isolated according to protocols published previously. Total cellular RNA was extracted and hybridized onto an HU133 Plus 2.0 GeneChip (Affymetrix) according to the manufacturer’s recommendations.

2012-03-26 | E-GEOD-36809 | biostudies-arrayexpress

A Genomic Score Prognostic of Outcome in Trauma Patients

Project description:Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. Contributor: The Inflammation and the Host Response to Injury Large Scale Collaborative Research Program Keywords: expression profiles cRNA derived from whole blood leukocytes obtained within 12 hours of hospital admission provided gene expression data for the entire genome that were used to create a gene expression score for each patient. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 hours following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE and ISS scores with outcome.

2009-04-12 | E-GEOD-11375 | biostudies-arrayexpress

A Genomic Score Prognostic of Outcome in Trauma Patients

2009-04-13 | GSE11375 | GEO

ARDSProfiling

Project description:To investigate immunologic alterations taking place in patients with nosocomial sepsis, we undertook genomic expression analysis of white blood cells (WBC) using DNA microarrays in a small sample of trauma patients who developed severe sepsis/septic shock during their ICU stay and compared with trauma patients with uncomplicated sepsis. RNA was extracted from blood obtained upon admission (a) and at the onset of the disease (b).

2012-08-01 | E-MEXP-3621 | biostudies-arrayexpress

Whole transcriptome analysis of lung tissue from mice after thoraxtrauma with and without sEV biogenesis inhibitor GW4869

Project description:To assess trauma associated gene expression signatures in lungs after thorax trauma mediated by small extracellular vesicles (sEVs) total RNA was isolated from lung lysates of mice after experimental blunt chest trauma with/without intravenous injection of GW4869 (2µg/g body weight).

2021-04-17 | GSE172209 | GEO

Expression data for C. elegans blunt force trauma

Project description:C. elegans exhibit an age-dependent mechanical stress response to blunt force injury. Stress responses are often defined in part by an elicited cellular transcriptional response. We find in C. elegans that mechanical stress by blunt trauma induces a distinct and age-dependent transcriptional program.

2020-04-09 | GSE148325 | GEO

Adoptively transferred in vitro-generated MDSCs improve T cell function and antigen-specific immunity after blunt chest trauma-induced lung injury

Project description:Does the adoptive transfer of MDSCs modulate lymphocyte (T cell) functions? Microarray expression analysis of T cells from MDSC-treated mice after Blunt chest trauma (TxT)

2022-06-16 | GSE188171 | GEO

Regulation of the transcriptional response to mechanical trauma by vhp-1

Project description:Mechanical stress by blunt force trauma elicits a distinct and reproducible transcriptional response in C. elegans. Vhp-1, a MAPK phosphatase, regulates a significant portion of these stress-inducible transcripts.

2020-04-09 | GSE148337 | GEO

Expression data for C. elegans blunt force trauma

Project description:Expression data for C. elegans blunt force trauma

| PRJNA623896 | ENA

Cell Specific Expression & Pathway Analyses Reveal Novel Alterations in Trauma-Related Human T-Cell & Monocyte Pathways

Project description:Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for medicine’s future. Patients with injury severe enough to develop multiple organ dysfunction syndrome (MODS) are known to have multiple immune derangements, including T-cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly-enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers a previously unavailable opportunity to discover novel leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in the T-cell, monocyte, and total leukocyte transcriptome, with only 12% of these genomic changes common to all three cell populations. T-cell-specific pathway analyses identified increased gene expression of several novel inhibitory receptors (PD-1, CD152, NRP-1, Lag3), and concomitant decreases in stimulatory receptors (CD28, CD4, IL-2Ralpha). Functional analysis of T-cells and monocytes confirmed reduced T-cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly-enriched cell populations combined with knowledge-based pathway analyses leads to the identification of novel regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell specific pathway analyses can be used to discover novel pathway alterations in human disease. Keywords: Gene expression profiling of circulating total blood leukocytes, T-Cells, and Monocytes in severe trauma patients and healthy subjects.

2006-09-15 | GSE5580 | GEO

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