Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Feb;80(2):250-7.
doi: 10.1097/TA.0000000000000905.

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults

Ravi F Sood  1 , Nicole S Gibran, Brett D Arnoldo, Richard L Gamelli, David N Herndon, Ronald G Tompkins; Inflammation the Host Response to Injury Investigators
Affiliations

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults

Ravi F Sood et al. J Trauma Acute Care Surg. 2016 Feb.

Abstract

Background: In the patient with burn injury, older age, larger percentage of total body surface area (TBS) burned, and inhalation injury are established risk factors for death, which typically results from multisystem organ failure and sepsis, implicating burn-induced immune dysregulation as a contributory mechanism. We sought to identify early transcriptomic changes in circulating leukocytes underlying increased mortality associated with these three risk factors.

Methods: We performed a retrospective analysis of the Glue Grant database. From 2003 to 2010, 324 adults with 20% or greater TBS burned were prospectively enrolled at five US burn centers, and 112 provided blood samples within 1 week after burn. RNA was extracted from pooled leukocytes for hybridization onto Affymetrix HU133 Plus 2.0 GeneChips. A multivariate regression model was constructed to determine risk factors for mortality. Testing for differential gene association associated with age, burn size, and inhalation injury was based on linear models using a fold change threshold of 1.5 and false discovery rate of 0.05.

Results: After adjusting for potential confounders, age greater than 60 years (relative risk [RR], 4.53; 95% confidence interval [CI], 2.93-6.99), burn size greater than 40% TBS (RR, 4.24; 95% CI, 2.61-6.91), and inhalation injury (RR, 2.08; 95% CI, 1.35-3.21) were independently associated with mortality. No genes were differentially expressed in association with age greater than 60 years or inhalation injury. Fifty-one probe sets representing 39 unique genes were differentially expressed in leukocytes from patients with burn size greater than 40% TBS; these genes were associated with platelet activation and degranulation/exocytosis, and gene-set enrichment analysis suggested increased cellular proliferation and down-regulation of proinflammatory cytokines.

Conclusion: Among adults with large burns, older age, increasing burn size, and inhalation injury have a modest effect on the leukocyte transcriptome in the context of the "genomic storm" induced by a 20% or greater than TBS burned. The 39-gene signature we identified may provide novel targets for the development of therapies to reduce morbidity and mortality associated with burns greater than 40% TBS.

Level of evidence: Epidemiologic study, level III.

PubMed Disclaimer

Conflict of interest statement

Disclosure:

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Heat map of 51 probe sets differentially expressed in whole-blood leukocytes isolated from patients with burn size >40% total body surface area (TBSA). Columns represent individual patient samples, ordered from left to right by increasing %TBSA burned. Each row represents one probe set that was differentially expressed in association with >40% TBSA burn after adjusting for age and inhalation injury; rows were ordered by hierarchical clustering. Expression values are scaled in the row direction, with red indicating relatively high expression and blue relatively low expression.
FIGURE 2
FIGURE 2
Gene network based on the 39 unique genes differentially regulated in whole-blood leukocytes isolated from patients with burn size >40% total body surface area (TBSA). Nodes represent gene products, with black circles indicating genes identified in our differential-expression analysis and gray circles indicating related genes. For related genes (gray circles), node size is proportional to the gene score assigned by GeneMANIA. Line thickness is proportional to the weight of the link, and line color indicates the type of link: purple, co-expression; pink, physical interaction; blue, co-localization; and cyan, participation in a common reaction within a pathway.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Branski LK, Herndon DN, Barrow RE. A brief history of acute burn care management. In: Herndon DN, editor. Total Burn Care. 4. Philadelphia, PA: Saunders; 2012. pp. 1–9.
    1. Peck MD. Epidemiology of burns throughout the world. Part I: Distribution and risk factors. Burns. 2011;37(7):1087–100. - PubMed
    1. Bull JP, Squire JR. A Study of Mortality in a Burns Unit: Standards for the Evaluation of Alternative Methods of Treatment. Ann Surg. 1949;130(2):160–73. - PMC - PubMed
    1. Hussain A, Choukairi F, Dunn K. Predicting survival in thermal injury: a systematic review of methodology of composite prediction models. Burns. 2013;39(5):835–50. - PubMed
    1. Taylor SL, Lawless M, Curri T, Sen S, Greenhalgh DG, Palmieri TL. Predicting mortality from burns: the need for age-group specific models. Burns. 2014;40(6):1106–15. - PMC - PubMed

Publication types