title: Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study.
abstract: BACKGROUND
  Blood transfusion in the perioperative period has frequently been associated with an excess of nosocomial infections. Whilst transfused whole blood induces specific host immune alteration that may predispose to nosocomial infections, the immunomodulating properties associated with leukodepleted blood remain incompletely understood. In this study, we explore the hypothesis that the transfusion of leukodepleted allogeneic blood during or following major gastrointestinal surgery is associated with an immunosuppressed phenotype, which may in turn predispose to postoperative infectious complications.
  
  
  METHODS
  Patients aged over 45 years undergoing scheduled inpatient major gastrointestinal surgery were recruited. Gene expression profiles of specific inflammatory genes were assayed from blood collected preoperatively, at 24 and at 48 hours after surgery. Genes were selected based on their ability to represent specific immune pathways. Gene expression was quantified using quantitative real-time polymerase chain reaction (qRT-PCR) to measure messenger RNA (mRNA) levels. Postoperative infections were documented using predefined criteria.
  
  
  RESULTS
  One hundred and nineteen patients were recruited. Fifteen (13%) patients required blood transfusion within 24 hours of surgery, 44 (37%) patients developed infections and 3 (2%) patients died prior to discharge. Patients receiving a blood transfusion were more likely to develop postoperative infections (P =0.02) and to have lower tumour necrosis factor alpha (TNFα), interleukin (IL)-12, IL-23 and RAR-related orphan receptor gamma T (RORγt) gene expression in the postoperative period (P <0.05). The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving a blood transfusion over this period. Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult.
  
  
  CONCLUSIONS
  An association between an immunosuppressive pattern of gene expression and blood transfusion following major elective gastrointestinal surgery is described. This gene expression profile includes a reduction in the activity of innate immunity and T helper cell type 1 (Th1) and T helper cell type 17 (Th17) pathways in those patients receiving a blood transfusion. Blood transfusion was also associated with an excess of infectious complications in this cohort. A mechanistic link is suggested but not proven.
authors.forename: Paraskevi C
authors.initials: PC
authors.lastname: Fragkou
authors.forename: Hew D
authors.initials: HD
authors.lastname: Torrance
authors.forename: Rupert M
authors.initials: RM
authors.lastname: Pearse
authors.forename: Gareth L
authors.initials: GL
authors.lastname: Ackland
authors.forename: John R
authors.initials: JR
authors.lastname: Prowle
authors.forename: Helen C
authors.initials: HC
authors.lastname: Owen
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Hinds
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Dwyer
mesh_terms: D000368:Aged; D003428:Cross Infection / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D013505:Digestive System Surgical Procedures; D004198:Disease Susceptibility / Q000276:immunology; D017558:Elective Surgical Procedures; D005260:Female; D015870:Gene Expression; D017052:Hospital Mortality; D006801:Humans; D007108:Immune Tolerance; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D059035:Perioperative Period; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D065227:Transfusion Reaction
chemical_list: D016207:Cytokines; D012333:RNA, Messenger