An Integrated Clinico-transcriptomic Approach Identifies a Central Role of the Heme Degradation Pathway for Septic Complications after Trauma. Issue 6 (December 2016)

• Record Type: Journal Article
• Authors: Rittirsch, Daniel; Schoenborn, Veit; Lindig, Sandro; Wanner, Elisabeth; Sprengel, Kai; Günkel, Sebastian; Blaess, Markus; Schaarschmidt, Barbara; Sailer, Patricia; Märsmann, Sonja; Simmen, Hans-Peter; Cinelli, Paolo; Bauer, Michael; Claus, Ralf A.; Wanner, Guido A.
• Is Part Of: Annals of surgery. Volume 264:Issue 6(2016:Dec.)
• Page Start: 1125
• Page End: 1134
• Publication Date: 2016-12
• Subjects: heme degradation pathway -- multiple injury -- sepsis -- systemic inflammation -- transcriptome profiling -- trauma; Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000001553
• Languages: English
• ISSNs: 0003-4932

Abstract

Abstract : Supplemental Digital Content is available in the text Abstract : Objective: The present study was aimed to identify mechanisms linked to complicated courses and adverse events after severe trauma by a systems biology approach. Summary Background Data: In severe trauma, overwhelming systemic inflammation can result in additional damage and the development of complications, including sepsis. Methods: In a prospective, longitudinal single-center study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ≥17 points; n = 81) were analyzed for dynamic changes in gene expression over a period of 21 days by whole-genome screening (discovery set; n = 10 patients; 90 samples) and quantitative RT-PCR (validation set; n = 71 patients, 517 samples). Multivariate correlational analysis of transcripts and clinical parameters was used to identify mechanisms related to sepsis. Results: Transcriptome profiling of the discovery set revealed the strongest changes between patients with either systemic inflammation or sepsis in gene expression of the heme degradation pathway. Using quantitative RT-PCR analyses (validation set), the key components haptoglobin (HP), cluster of differentiation (CD) 163, heme oxygenase-1 (HMOX1), and biliverdin reductase A (BLVRA) showed robust changes following trauma. Upregulation of HP was associated with the severity of systemic inflammation and the development of sepsis. Patients who received allogeneic blood transfusions had a higher incidence of nosocomial infections and sepsis, and the amount of blood transfusion as source of free heme correlated with the expression pattern of HP. Conclusions: These findings indicate that the heme degradation pathway is associated with increased susceptibility to septic complications after trauma, which is indicated by HP expression in particular.