Transcriptomic Changes Within Human Bone Marrow After Severe Trauma.

ABSTRACT

BACKGROUND: Severe trauma is associated with severe systemic inflammation and neuroendocrine activation that is associated with erythroid progenitor growth suppression and refractory anemia. Although distinct transcriptional profiles have been detected in numerous tissue types after trauma, no study has yet characterized this within the bone marrow. This study sought to identify a unique bone marrow transcriptomic response following trauma. METHODS: In a prospective observational cohort study, bone marrow was obtained from severely injured trauma patients with a hip or femur fracture (n = 52), elective hip replacement patients (n = 33), and healthy controls (n = 11). RNA was isolated from bone marrow using a Purelink RNA mini kit. Direct quantification of mRNA copies was performed by NanoString Technologies on a custom gene panel. RESULTS: Trauma patients displayed an upregulation of genes encoding receptors known to have inhibitory downstream effects on erythropoiesis, including ferroportin, interleukin-6 (IL-6) receptor, transforming growth factor-beta (TGF-ß) receptor, and IL-10, as well as genes involved in innate immunity including toll-like receptor 4 (TLR4)-mediated signaling factors. In contrast, hip replacement patients had downregulated transcription of IL-1ß, IL-6, TGF-ß, tumor necrosis factor alpha, and the HAMP gene with no change in TLR4-mediated signaling factors. CONCLUSIONS: A unique transcriptomic response within the bone marrow was identified following severe trauma compared to elective hip replacement. These transcriptomic differences were related to the innate immune response as well as known inhibitors of erythropoiesis. Although confined to just one time point, this differential transcriptional response may be linked to refractory anemia and inflammation after injury.