Association Between Gene Expression Biomarkers of Immunosuppression and Blood Transfusion in Severely Injured Polytrauma Patients

Ann Surg. 2015 Apr;261(4):751-9. doi: 10.1097/SLA.0000000000000653.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bacteremia / epidemiology
  • Biomarkers / metabolism
  • Blood Transfusion*
  • Causality
  • Comorbidity
  • Contraindications
  • Cross Infection / epidemiology*
  • Cytokines / genetics
  • Cytokines / immunology
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Fungemia / epidemiology
  • GATA3 Transcription Factor / genetics
  • GATA3 Transcription Factor / metabolism
  • Gene Expression
  • Humans
  • Immune Tolerance / immunology*
  • Injury Severity Score
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism*
  • Interleukin-27 / genetics
  • Interleukin-27 / metabolism*
  • Male
  • Multiple Trauma / epidemiology
  • Multiple Trauma / immunology*
  • Multiple Trauma / therapy*
  • Multivariate Analysis
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / genetics
  • Nuclear Receptor Subfamily 1, Group F, Member 3 / metabolism
  • Phenotype
  • RNA, Messenger / isolation & purification
  • T-Lymphocytes, Helper-Inducer / immunology
  • Transcription Factors / genetics
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Interleukin-27
  • Nuclear Receptor Subfamily 1, Group F, Member 3
  • RNA, Messenger
  • Transcription Factors
  • Interleukin-10