Burn wounds in the young versus the aged patient display differential immunological responses

Farinas, Angel; Bamba, Ravinder; Pollins, Alonda C.; Cardwell, Nancy L.; Nanney, Lillian B.; Thayer, Wesley P.

doi:10.1016/j.burns.2018.05.012

Cited by 24 publications

(7 citation statements)

References 38 publications

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“…A prior study compared cytokine responses between young and elderly burn patients. They elucidated that at least 2 cytokines, CCL5 and EGF, are downregulated in elderly burn patients[27]. Consistent with this finding, we report here that five genes involved in EGF signaling (associated with wound healing) are significantly downregulated in high TBSA elderly burn patients (S2 Table).…”

Section: Discussionsupporting

confidence: 91%

Genome-wide comparisons of gene expression in adult versus elderly burn patients

et al. 2019

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PurposeMortality and morbidity rates of elderly burn patients remain high despite numerous advancements in modern burn care. While prior studies have offered first insights on the biochemical changes in elderly burn patients compared to adults, the underlying cellular responses remain largely unknown. In this study, we aim to characterize the transcriptome of elderly burn patients and compare it to adult burn patients to obtain insights into the underlying molecular responses post-burn and to elucidate the effect of advanced age on the acute burn response.Materials and methodsMicroarray data obtained from the Glue Grant Trauma-Related Database was obtained from blood specimens for ten elderly patients (n = 10), each with a set of two sex and total body surface area (TBSA) matched adult controls (n = 20), during the acute phase post-burn. Adult and elderly demographics and clinical outcomes were contrasted using using the Chi-Square test, Fisher’s Exact Test, or two-sample t-tests, as appropriate (p<0.05). Enrichment and heat maps were generated to compare gene expression in elderly versus adult burn patients.ResultsSupervised analysis identified multiple genes that were differentially expressed between the elderly and adult groups. Pathway analysis and heatmap generation suggest that elderly patients share a distinct hypo-inflammatory response in the acute post-burn phase with downregulation of a number of immune-related pathways, including those related to antigen processing, specifically via MHC class I, ubiquitination and proteasome degradation (p<0.001, FDR < .001). Cell signalling pathways, such as NF-κB, C-type lectin receptor, and T cell receptor signalling were also significantly downregulated in elderly burn patients, as well as those relating to antiviral immunity (p<0.001, FDR < .001). Many genes which were observed to be upregulated in elderly patients with high TBSA burn injuries were associated with destruction-related cellular pathways such as complement activation and immunoglobulin production (p<0.005, FDR <0.01).ConclusionsThe altered inflammatory and immune responses at the transcriptome level in elderly patients after burn are indicative of a failure in elderly burn patients to initiate an appropriate inflammatory and stress response during the acute phase post-burn.

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Section: Discussionsupporting

confidence: 91%

Genome-wide comparisons of gene expression in adult versus elderly burn patients

et al. 2019

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“…Immunological responses in burn injuries differ with age. A clinical study revealed a trend in which elderly patients expressed higher levels of pro-inflammatory cytokines but contained fewer macrophage counts in the wound bed when compared to the younger group [502]. Although the authors did not evaluate the wound re-epithelialization, they did show a trend in which older patients were associated with a higher burn severity score index when compared to the younger patients.…”

Section: Skin Immune Responses In Wound Healingmentioning

confidence: 99%

The Dynamics of the Skin’s Immune System

Nguyen

Soulika

2019

IJMS

465

339

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The skin is a complex organ that has devised numerous strategies, such as physical, chemical, and microbiological barriers, to protect the host from external insults. In addition, the skin contains an intricate network of immune cells resident to the tissue, crucial for host defense as well as tissue homeostasis. In the event of an insult, the skin-resident immune cells are crucial not only for prevention of infection but also for tissue reconstruction. Deregulation of immune responses often leads to impaired healing and poor tissue restoration and function. In this review, we will discuss the defensive components of the skin and focus on the function of skin-resident immune cells in homeostasis and their role in wound healing.

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“…CCL5 is a chemokine that plays a role in the peripheral immune system, it helps regulate synaptic activity, and it protects against a variety of neurotoxins [41]. There is evidence that CCL5 is expressed in the skin after burns and may constitute a drug target [42,43]. On the other hand, LCK is involved in the development, function, and differentiation of T cells [44].…”

Section: Discussionmentioning

confidence: 99%

Altered Genes and Biological Functions in Response to Severe Burns

Liu¹,

Rong²,

Huang

et al. 2021

BioMed Research International

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Severe burns are acute wounds caused by local heat exposure, resulting in life-threatening systemic effects and poor survival. However, the specific molecular mechanisms remain unclear. First, we downloaded gene expression data related to severe burns from the GEO database (GSE19743, GSE37069, and GSE77791). Then, a gene expression analysis was performed to identify differentially expressed genes (DEGs) and construct protein-protein interaction (PPI) network. The molecular mechanism was identified by enrichment analysis and Gene Set Enrichment Analysis. In addition, STEM software was used to screen for genes persistently expressed during response to severe burns, and receiver operating characteristic (ROC) curve was used to identify key DEGs. A total of 2631 upregulated and 3451 downregulated DEGs were identified. PPI network analysis clustered these DEGs into 13 modules. Importantly, module genes mostly related with immune responses and metabolism. In addition, we identified genes persistently altered during the response to severe burns corresponding to survival and death status. Among the genes with high area under the ROC curve in the PPI network gene, CCL5 and LCK were identified as key DEGs, which may affect the prognosis of burn patients. Gene set variation analysis showed that the immune response was inhibited and several types of immune cells were decreased, while the metabolic response was enhanced. The results showed that persistent gene expression changes occur in response to severe burns, which may underlie chronic alterations in physiological pathways. Identifying the key altered genes may reveal potential therapeutic targets for mitigating the effects of severe burns.

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Burn wounds in the young versus the aged patient display differential immunological responses

Cited by 24 publications

References 38 publications

Genome-wide comparisons of gene expression in adult versus elderly burn patients

Genome-wide comparisons of gene expression in adult versus elderly burn patients

The Dynamics of the Skin’s Immune System

Altered Genes and Biological Functions in Response to Severe Burns

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