BACKGROUND: No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, non-invasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients. METHODS: This prospective observational study enrolled two patient cohorts within a single Burn Center into an institutionally-approved IRB study. Blood draws were performed <48 hours after injury. Initial unbiased immune gene expression analysis compared 23 burn patients and 6 healthy controls using multiplex immune gene expression analysis of RNA from peripheral blood mononuclear cells (PBMC). We then performed cconfirmatory outcomes analysis in 109 burn patients and 19 healthy controls using a targeted rapid qtPCR. Findings were validated and modeled associations with clinical outcomes using a regression model. RESULTS: 149 genes with a significant difference in expression from burn patients compared to controls were identified. Pathway Analysis identified pathways related to IL-10 and inducible nitric oxide synthase (iNOS) signaling to have significant z-scores. qPCR analysis of IL-10, IL-12, arginase-1 (ARG1), and iNOS demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of NOS2 and IL-12. Burn severity, acute lung injury (ALI), development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2 and (ARG1 + IL-10)/(NOS2 + IL-12) transcript levels further improved the correlation with outcomes. Using a multivariate regression model, adjusting for patient confounders demonstrated that (ARG1 + IL-10)/(NOS2 + IL-12) significantly correlated with burn severity and development of ALI. CONCLUSIONS: We present a means to predict patient outcomes early after burn injury using peripheral blood, allowing early identification of underlying immune dysfunction. LEVEL OF EVIDENCE: Level 1 Prognostic and Epidemiological Study.
BACKGROUND: No methods exist to rapidly and accurately quantify the immune insult created by burn injuries. The development of a rapid, non-invasive clinical biomarker assay that evaluates a burn patient's underlying immune dysfunction and predicts clinical outcomes could transform burn care. We aimed to determine a set of peripheral biomarkers that correlates with clinical outcomes of burn patients. METHODS: This prospective observational study enrolled two patient cohorts within a single Burn Center into an institutionally-approved IRB study. Blood draws were performed <48 hours after injury. Initial unbiased immune gene expression analysis compared 23 burn patients and 6 healthy controls using multiplex immune gene expression analysis of RNA from peripheral blood mononuclear cells (PBMC). We then performed cconfirmatory outcomes analysis in 109 burn patients and 19 healthy controls using a targeted rapid qtPCR. Findings were validated and modeled associations with clinical outcomes using a regression model. RESULTS: 149 genes with a significant difference in expression from burn patients compared to controls were identified. Pathway Analysis identified pathways related to IL-10 and inducible nitric oxide synthase (iNOS) signaling to have significant z-scores. qPCR analysis of IL-10, IL-12, arginase-1 (ARG1), and iNOS demonstrated that burn injury was associated with increased expression of ARG1 and IL-10, and decreased expression of NOS2 and IL-12. Burn severity, acute lung injury (ALI), development of infection, failure of skin autograft, and mortality significantly correlated with expression of one or more of these genes. Ratios of IL-10/IL-12, ARG1/NOS2 and (ARG1 + IL-10)/(NOS2 + IL-12) transcript levels further improved the correlation with outcomes. Using a multivariate regression model, adjusting for patient confounders demonstrated that (ARG1 + IL-10)/(NOS2 + IL-12) significantly correlated with burn severity and development of ALI. CONCLUSIONS: We present a means to predict patient outcomes early after burn injury using peripheral blood, allowing early identification of underlying immune dysfunction. LEVEL OF EVIDENCE: Level 1 Prognostic and Epidemiological Study.
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