title: Association between gene expression biomarkers of immunosuppression and blood transfusion in severely injured polytrauma patients.
abstract: OBJECTIVE
  To explore the hypothesis that blood transfusion contributes to an immunosuppressed phenotype in severely injured patients.
  
  
  BACKGROUND
  Despite trauma patients using disproportionately large quantities of blood and blood products, the immunomodulatory effects of blood transfusion in this group are inadequately described.
  
  
  METHODS
  A total of 112 ventilated polytrauma patients were recruited. Messenger RNA (mRNA) was extracted from PAXGene tubes collected within 2 hours of the trauma, at 24 hours, and at 72 hours. T-helper cell subtype specific cytokines and transcription factors were quantified using real-time polymerase chain reaction.
  
  
  RESULTS
  Median injury severity score was 29. Blood transfusion was administered to 27 (24%) patients before the 2-hour sampling point. Transfusion was associated with a greater immediate rise in IL-10 (P = 0.003) and IL-27 (P = 0.04) mRNA levels. Blood products were transfused in 72 (64%) patients within the first 24 hours. There was an association between transfusion at 24 hours and higher IL-10 (P < 0.0001), lower Foxp3 (P = 0.01), GATA3 (P = 0.006), and RORγt (P = 0.05) mRNA levels at 24 hours. There were greater reductions in T-bet (P = 0.03) mRNA levels and lesser increases in TNFα (P = 0.015) and IFNγ (P = 0.035) at 24 hours in those transfused. Multiple regression models confirmed that the transfusion of blood products was independently associated with altered patterns of gene expression. Blood stream infections occur in 15 (20.8%) of those transfused in the first 24 hours, compared with 1 patient (2.5%) not transfused (OR = 10.3 [1.3-81], P = 0.008).
  
  
  CONCLUSIONS
  The primarily immunosuppressive inflammatory response to polytrauma may be exacerbated by the transfusion of blood products. Furthermore, transfusion was associated with an increased susceptibility to nosocomial infections.
authors.affiliation: *Adult Critical Care Unit, Royal London Hospital, Barts Health NHS Trust, London †Centre for Trauma Sciences, Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London ‡Centre for Translational Medicine and Therapeutics, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London §Genome Centre, John Vane Science Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London, United Kingdom.
authors.forename: Hew Dt
authors.initials: HD
authors.lastname: Torrance
authors.forename: Karim
authors.initials: K
authors.lastname: Brohi
authors.forename: Rupert M
authors.initials: RM
authors.lastname: Pearse
authors.forename: Charles A
authors.initials: CA
authors.lastname: Mein
authors.forename: Eva
authors.initials: E
authors.lastname: Wozniak
authors.forename: John R
authors.initials: JR
authors.lastname: Prowle
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Hinds
authors.forename: Michael J
authors.initials: MJ
authors.lastname: OʼDwyer
mesh_terms: D000328:Adult; D016470:Bacteremia / Q000453:epidemiology; D015415:Biomarkers / Q000378:metabolism; D001803:Blood Transfusion; D015984:Causality; D015897:Comorbidity; D000075202:Contraindications; D003428:Cross Infection / Q000453:epidemiology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D016469:Fungemia / Q000453:epidemiology; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D015601:Injury Severity Score; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D064094:Interleukin-27 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009104:Multiple Trauma / Q000453:epidemiology / Q000276:immunology* / Q000628:therapy*; D015999:Multivariate Analysis; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000302:isolation & purification; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D064094:Interleukin-27; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D014157:Transcription Factors; D016753:Interleukin-10