Determination of Burn Patient Outcome by Large-Scale Quantitative Discovery Proteomics

Abstract

Objective Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry (LC-MS) and multiplex cytokine analysis to profile the plasma proteome of survivors and non-survivors of massive burn injury to determine the proteomic survival signature following a major burn injury. Design Proteomic discovery study. Setting Five burn hospitals across the U.S. Patients Thirty-two burn patients (16 non-survivors and 16 survivors), 19–89 years of age, were admitted within 96 h of injury to the participating hospitals with burns covering >20% of the total body surface area and required at least one surgical intervention. Interventions None. Measurements and Main Results We found differences in circulating levels of 43 proteins involved in the acute phase response, hepatic signaling, the complement cascade, inflammation, and insulin resistance. Thirty-two of the proteins identified were not previously known to play a role in the response to burn. IL-4, IL-8, GM-CSF, MCP-1, and β2-microglobulin correlated well with survival and may serve as clinical biomarkers. Conclusions These results demonstrate the utility of these techniques for establishing proteomic survival signatures and for use as a discovery tool to identify candidate biomarkers for survival. This is the first clinical application of a high-throughput, large-scale LC-MS-based quantitative plasma proteomic approach for biomarker discovery for the prediction of patient outcome following burn, trauma or critical illness.

The blister fluid proteome of paediatric burns

“…Some previously reported candidate biomarkers of burn injury such as C-reactive protein [17], SCCA1/SCCA2 [16], gelsolin [16], IQGAP1 [16], Lactate dehydrogenase B [16], leukocyte elastase inhibitor [16], haptoglobin [16], HSP 90 [16], haemoglobin [37], β2-Microglobulin [18], apolipoprotein A [18], Coagulation factor X [18], prothrombin [18], complement C8 and C9 [18], antithrombin 3 [18], and plasminogen [18] were also identified in this study (Table 4). More interestingly, some of these proteins were only detected in one or two of the burn depth categories examined.…”

“…A considerable number of burn injury studies have focused on the examination of biopsy and debrided hyperplastic tissue [15,16] or blood samples [17][18][19] from patients to evaluate underlying biology. However, tissue and blood collection are both highly invasive approaches and distressful for children.…”

“…injury have discovered significant abundance changes in proteins associated with: cellular signalling; inflammatory mediation; response to acute stress and injury; inflammatory and immune response; cellular integrity maintenance; and cytoskeletal formation [16][17][18][19][23][24][25].…”

Patterns of gene expression among murine models of hemorrhagic shock/trauma and sepsis

“…Whether this represents an evolutionary benefit to the host, by trying to reduce the likelihood of an autoimmune response to released damaged cell products or organ injury, or a period of increased host susceptibility after the initial emergency myelopoiesis response, has yet to be determined. Unfortunately, animal welfare issues prevent us from determining how long it truly takes the juvenile and elderly mouse to return to baseline genomic expression patterns, but preliminary data in elderly humans may indicate that the process may not be rapid (11,14).…”

Evaluation of haemoglobin in blister fluid as an indicator of paediatric burn wound depth

“…To date few quantitative biological indicators or markers have been investigated for skin related conditions or specifically for burn wounds. Burn patient serum has been investigated for biomarkers predicting survival in severely burnt patients [9]; but as the incidence of burn mortality in Australia is relatively low, the majority of paediatric patients presenting to Australian burn centres do not face these survival concerns [10,11]. Studies focussing on biomarkers that could assist in predicting cutaneous wound healing trajectories have predominantly been conducted with the aim of assessing chronic non-healing wounds rather than acute wounds [12][13][14][15].…”