Temporal expression of circulating miRNA after severe injury.

BACKGROUND: Severe injury can lead to immune dysfunction and predispose patients to infection and death. Micro-RNAs regulate gene expression and may act as biomarkers for susceptibility to infection. The aim of this study was to examine the temporal and differential expression of previously identified dysregulated micro-RNAs in patients with severe injury.

METHODS: Fourteen severely injured patients requiring transfusion were enrolled prospectively in this study approved by our institutional review board. Inclusion criteria consisted of adult patients deemed clinically to be in hemorrhagic shock necessitating transfusion in the acute phase of their injury care. Peripheral blood samples were obtained after admission to the surgical intensive care unit and again at 6, 12, 24, and 48 hours after admission. The samples obtained at arrival to the intensive care unit and 24 and 48 hours later were analyzed in this data set. Fourteen healthy volunteers served as controls. The 10 dysregulated micro-RNAs identified in a prior study at the 12-hour time point and important genes in innate immunity were measured using quantitative reverse transcription-polymerase chain reaction.

RESULTS: The participants were 21-77 years old (median, 42), 78% were male, and their Injury Severity Score ranged from 11 to 43 (median, 27); 11 had blunt and 3 had penetrating injuries. Three were intubated and 5 had received blood products before arrival at the hospital. Base deficit on hospital admission was 3-20 (median, 9). All patients required blood transfusion secondary to blood loss sustained during injury. Eleven of the 14 patients went directly to the operating room from the emergency department for control of the source of hemorrhage. Survival to discharge was 93%. Seven patients developed infection. Compared with healthy controls, miR-106a was downregulated at all time points compared with controls (P < .05). miR-618 was upregulated in initial blood draws (P < .05) and at 24 and 48 hours (P < .06). Tumor necrosis factor α and human leukocyte antigen-DR (HLA-DR) were downregulated, and interleukin-10 and PD-L1 were upregulated (P < .05). In patients who developed infection, miR-106a levels appeared more downregulated than those who did not develop infection.

CONCLUSION: miR-106a was downregulated in trauma patients after major injury for up to 48 hours after intensive care unit admission. Tumor necrosis factor α and interleukin-10 are targeted by miR-106a, which are regulators of the immune response. Manipulation of micro-RNA expression may be a therapeutic target for immune dysfunction.