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Impaired Immune Response in Elderly Burn Patients: New Insights Into the Immune-senescence Phenotype.

ABSTRACT: OBJECTIVE:Comparing the inflammatory and immunological trajectories in burned adults versus burned elderly patients to gain novel insights and better understanding why elderly have poor outcomes. SUMMARY BACKGROUND DATA:Despite receiving the same treatment and clinical consideration as all other burn patients, elderly patients continue to have substantially poorer outcomes compared with adults. In light of an aging population, gaining a better understanding of their susceptibility to complications and creating new treatment strategies is imperative. METHODS:We included 130 burn patients (94 adults: <65 years old and 36 elderly: ?65 years old) and 10 healthy controls in this study. Immune activity and expression was assessed using bioplex at various time points. Clinical outcomes such as infection, sepsis, and mortality were prospectively collected. RESULTS:Elderly burn patients had significantly lower burn size but significantly higher Baux scores. Morbidity and mortality was significantly increased in the elderly cohort. Immune biomarkers indicated that elderly are immune compromised and unable to respond with the expected inflammatory response during the early phase after injury. This trajectory changes to a hyperinflammatory pattern during the later phase after burn. These findings are even more pronounced when comparing sepsis versus nonsepsis patients as well as survivors versus nonsurvivors in the elderly. CONCLUSIONS:Elderly burned patients mount a delayed immune and dampened inflammatory response early after burn injury that changes to an augmented response at later time points. Late-onset sepsis and nonsurvivors had an immune exhaustion phenotype, which may represent one of the main mediators responsible for the striking mortality in elderly.

SUBMITTER: Stanojcic M

PROVIDER: S-EPMC4899096 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Impaired Immune Response in Elderly Burn Patients: New Insights Into the Immune-senescence Phenotype.

Stanojcic Mile M Chen Peter P Xiu Fangming F Jeschke Marc G MG

Annals of surgery 20160701 1

<h4>Objective</h4>Comparing the inflammatory and immunological trajectories in burned adults versus burned elderly patients to gain novel insights and better understanding why elderly have poor outcomes.<h4>Summary background data</h4>Despite receiving the same treatment and clinical consideration as all other burn patients, elderly patients continue to have substantially poorer outcomes compared with adults. In light of an aging population, gaining a better understanding of their susceptibility ...[more]

PMID: 26649579

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Project description: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.

Dataset Information

Impaired Immune Response in Elderly Burn Patients: New Insights Into the Immune-senescence Phenotype.

Publications

Impaired Immune Response in Elderly Burn Patients: New Insights Into the Immune-senescence Phenotype.

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