Early Transcriptomic Response to Burn injury: Severe Burns are Associated with Immune Pathway Shutdown
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ABSTRACT:
PROVIDER: PRJNA757018 | ENA |
REPOSITORIES: ENA
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Project description:Burn injury induces a systemic hyperinflammatory response with detrimental side effects. Studies have described the biochemical changes induced by severe burns, but the transcriptome response is not well characterized. The goal of this work is to characterize the blood transcriptome after burn injury. Burn patients presenting to a regional center between 2012-2017 were prospectively enrolled. Blood was collected on admission and at predetermined time points (hours 2, 4, 8, 12, 24). RNA was isolated and transcript levels were measured with a gene expression microarray. To identify differentially regulated genes (FDR≤0.1) by burn injury severity, patients were grouped by total body surface area (TBSA) above or below 20% and statistically enriched pathways were identified. Sixty-eight patients were analyzed, most patients were male with a median age of 41 (IQR, 30.5-58.5) years, and TBSA of 20% (11-34%). Thirty-five patients had %TBSA injury ≥20%, and this group experienced greater mortality (26% vs. 3%, p=0.008). Comparative analysis of genes from patients with </≥20% TBSA revealed 1505, 613, 380, 63, 1357, and 954 differentially expressed genes at hours 0, 2, 4, 8, 12 and 24 respectively. Pathway analysis revealed an initial upregulation in several immune/inflammatory pathways within the ≥20% TBSA groups followed by shutdown. Severe burn injury is associated with an early proinflammatory immune response followed by shutdown of these pathways. Examination of the immunoinflammatory response to burn injury through differential gene regulation and associated immune pathways by injury severity may identify mechanistic targets for future intervention.
2021-10-31 | GSE182616 | GEO
Project description:Severe burn injury is a one of the most devastating forms of trauma with over 1.1 million burns each year requiring medical attention in the United States. Deaths from burn injury are commonly caused by immune-related sequelae such as pneumonia, organ failure and other opportunistic bacterial infections. Though there have been numerous studies to assess the immunological dysfunction associated with burn injury, there have yet to be a predictive biomarker, that can be used to assess high risk patients and their outcomes. We hypothesized that circulating extracellular vesicles (EVs) released early after burn injury would promote activate peripheral macrophages and specific cargo could be used as a biomarker to identify at-risk patients. To test this hypothesis, we assessed the immune consequences of adoptive transfer of EVs isolated after burn injury in vitro and used unbiased proteomic on EVs from mouse models and human burn patients from the UNC Jaycee Burn Center. Findings here suggest EVs serve as mediators of immune dysfunction and potential biomarkers.
2022-02-16 | PXD028515 | Pride
Project description:To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury. Gene expression was measured using Affymetrix U133 Plus 2.0 arrays for both patient samples and healthy controls. Time points were binned into two groups: early stage for <11 days and middle stage for 11-49 days. 114 arrays for 57 patients (2 time points per patient) and 63 arrays for 63 healthy controls.
2010-06-16 | E-GEOD-19743 | biostudies-arrayexpress
Project description:To understand the age-dependent response to burn injury, blood samples from pediatric and adult patients were collected at different times after severe burn injury. Gene expression was measured using Affymetrix U133 Plus 2.0 arrays for both patient samples and healthy controls. Time points were binned into two groups: early stage for <11 days and middle stage for 11-49 days.
2010-06-03 | GSE19743 | GEO
Project description:scRNA and snATAC sequencing of cells harvested from the tendon injury site after a severe burn/tenotomy injury in Hoxa11 lineage traced mice allowed for differentation tracing of MSCs located in zeugopod after severe heterotopic ossification inducing injury. The use of immobilization also allowed us to determine the effects of limb immoblization on MSCs during aberrant wound healing.
2020-06-30 | GSE150995 | GEO
Project 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.
2017-07-02 | GSE77791 | GEO
Project description:Blood was sampled from severe burns patients over time as well as healthy subjects. Genome-wide expression analyses were conducted using the Affymetrix U133 plus 2.0 GeneChip™. The Inflammation and the Host Response to Injury Large-Scale Collaborative Research Program Blood was sampled from 244 severe burns patients over time as well as 35 healthy subjects who consented to blood sampling. Study subjects were treated under standard operating procedures to minimize treatment variations. Patients had burns covering >20% of the total body surface area and were admitted within 96 hours of injury. Genome-wide expression analyses were conducted using the Affymetrix U133 plus 2.0 GeneChip™.
2013-02-12 | E-GEOD-37069 | biostudies-arrayexpress
Project description:Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic co-morbidity and disease. To date, research has primarily focused on the systemic response severe injury, with little in the literature reported on impact of non-severe injuries (<15% total burn surface area; TBSA). To elucidate the metabolic consequences of non-severe burn injury, longitudinal plasma was collected from adults (n=35) who presented at hospital with a non-severe burn injury at admission, and at 6 week follow up. A cross-sectional baseline sample was also collected from non-burn control participants (n=14). Samples underwent multiplatform metabolic phenotyping using 1H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoproteins signatures and 852 lipid species from across 20 subclasses.
Multivariate data modelling (Orthogonal projection to latent structures-discriminate analysis) revealed alterations in lipoprotein and lipid metabolism when comparing baseline control to hospital admission samples, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value <1.0e-4), low density lipoprotein-2 subfractions (Variable importance in projection score; VIP >6.83e-1) and monoacyglyceride (20:4)(p-value <1.0e-4) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP >7.75e-1), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols and phosphatidylserines.
The results indicate a persistant systemic metabolic phenotype that occurs even in cases of non-severe burn injury. The phenotype is indicative of an accute inflammatory profile which continues to be sustained post-injury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have elevated incidence post- burn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify individual responses to injury, personalise intervention strtegies and improve acute care, reducing risk of chronic co-morbidity.
2023-07-19 | MSV000092486 | MassIVE
Project description:Background: Recent advances in proteome analysis technology and mass spectrometry have made it possible to identify and quantify many proteins at once. The aim of this study was to identify proteins associated with severe burn pathology using mass spectrometry and to elucidate a novel molecular pathology classification that will be clinically useful. Methods: In this single-centre, retrospective, observational study, blood samples were collected from patients with severe burns at two time points, on the day of injury and 1 week after injury. Proteins were measured using mass spectrometry, and then prognosis-related proteins were extracted via comparison of 28-day survivor and non-survivor groups. Enrichment and ROC (receiver operating characteristics) analyses were performed to evaluate the extracted proteins. Subsequently, these proteins were used to perform latent class analysis. Findings: Measurements were performed on 83 burn patients. In the non-survivor group, ten proteins were significantly altered on the day of injury, and these were associated with multiple metabolic and response processes to toxins. Of these ten proteins that underwent ROC curve analysis with 28-day death as the objective variable, HBA1, TTR, and SERPINF2 on the day of injury had an area under the curve >0.8. Latent class analysis of these three proteins classified them into three molecular pathotypes. Interpretation: Comprehensive mass spectrometry of plasma revealed that ten proteins were associated with prognosis in severe burns. Molecular pathotypes based on HBA1, TTR, and SERPINF2 were significantly associated with patient outcomes.
2023-07-10 | PXD043065 | Pride
Project description:Burn injuries are devastating traumas, often leading to life-long consequences that extend beyond the observable burn scar. Burn injury patients commonly develop chronic neurological disorders but the long-lasting impacts of burn injuries on neurons and glia in the brain is unknown. Whole transcriptome RNA-sequencing from cortical excitatory neurons, inhibitory neurons, astrocytes and microglia showed very few changes to the expression of genes with known functions five weeks following a non-severe burn injury in adult mice. However, genes related to GABA-A receptors in excitatory neurons and several cellular functions in microglia was found to be to differentially expressed in burn injured mice. These findings shed light on the long-term effect of burn injuries on the brain and may help identify potential therapeutic targets and windows to prevent neurological dysfunction in burn patients.
2024-02-15 | GSE229384 | GEO