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Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study.

Fragkou PC, Torrance HD, Pearse RM, Ackland GL, Prowle JR, Owen HC, Hinds CJ, O'Dwyer MJ - Crit Care (2014)

Bottom Line: One hundred and nineteen patients were recruited.Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult.A mechanistic link is suggested but not proven.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: 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.

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Related in: MedlinePlus

Perioperative blood transfusion and gene expression: Graphs A-H represent the mRNA levels of IL-12 at 24 hours, TNFα at 48 hours, IL-23 at 24 and 48 hours, RORγt at 24 and 48 hours and the ratio of TNFα/IL-10 at 24 and 48 hours following scheduled abdominal surgery in those patients that received a transfusion prior to this time point and in those patients that did not. Graphs represent median and 75th percentile. Results are expressed as a relative quantification ratio between the candidate and the reference genes. IL-10, interleukin 10; IL-12, interleukin 12; IL-23, interleukin 23; mRNA, messenger RNA; RORγt, RAR-related orphan receptor gamma T; TNFɑ, tumour necrosis factor alpha.
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Fig2: Perioperative blood transfusion and gene expression: Graphs A-H represent the mRNA levels of IL-12 at 24 hours, TNFα at 48 hours, IL-23 at 24 and 48 hours, RORγt at 24 and 48 hours and the ratio of TNFα/IL-10 at 24 and 48 hours following scheduled abdominal surgery in those patients that received a transfusion prior to this time point and in those patients that did not. Graphs represent median and 75th percentile. Results are expressed as a relative quantification ratio between the candidate and the reference genes. IL-10, interleukin 10; IL-12, interleukin 12; IL-23, interleukin 23; mRNA, messenger RNA; RORγt, RAR-related orphan receptor gamma T; TNFɑ, tumour necrosis factor alpha.

Mentions: On univariate analysis, IL-12 mRNA levels at 24 hours (P =0.02) and tumour necrosis factor alpha (TNFα) mRNA levels at 48 hours (P =0.01) were lower in those who received a blood transfusion in the first 24 hours postoperatively. IL-23 mRNA levels at 24 hours (P =0.007) and at 48 hours (P =0.03) and RAR-related orphan receptor gamma T (RORγt) mRNA levels at 24 hours (P =0.004) and at 48 hours (P =0.006) were lower in those receiving a blood transfusion over the first 24 hours postoperatively. The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving blood transfusion over this period (Figure 2A-H).Figure 2


Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study.

Fragkou PC, Torrance HD, Pearse RM, Ackland GL, Prowle JR, Owen HC, Hinds CJ, O'Dwyer MJ - Crit Care (2014)

Perioperative blood transfusion and gene expression: Graphs A-H represent the mRNA levels of IL-12 at 24 hours, TNFα at 48 hours, IL-23 at 24 and 48 hours, RORγt at 24 and 48 hours and the ratio of TNFα/IL-10 at 24 and 48 hours following scheduled abdominal surgery in those patients that received a transfusion prior to this time point and in those patients that did not. Graphs represent median and 75th percentile. Results are expressed as a relative quantification ratio between the candidate and the reference genes. IL-10, interleukin 10; IL-12, interleukin 12; IL-23, interleukin 23; mRNA, messenger RNA; RORγt, RAR-related orphan receptor gamma T; TNFɑ, tumour necrosis factor alpha.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4201915&req=5

Fig2: Perioperative blood transfusion and gene expression: Graphs A-H represent the mRNA levels of IL-12 at 24 hours, TNFα at 48 hours, IL-23 at 24 and 48 hours, RORγt at 24 and 48 hours and the ratio of TNFα/IL-10 at 24 and 48 hours following scheduled abdominal surgery in those patients that received a transfusion prior to this time point and in those patients that did not. Graphs represent median and 75th percentile. Results are expressed as a relative quantification ratio between the candidate and the reference genes. IL-10, interleukin 10; IL-12, interleukin 12; IL-23, interleukin 23; mRNA, messenger RNA; RORγt, RAR-related orphan receptor gamma T; TNFɑ, tumour necrosis factor alpha.
Mentions: On univariate analysis, IL-12 mRNA levels at 24 hours (P =0.02) and tumour necrosis factor alpha (TNFα) mRNA levels at 48 hours (P =0.01) were lower in those who received a blood transfusion in the first 24 hours postoperatively. IL-23 mRNA levels at 24 hours (P =0.007) and at 48 hours (P =0.03) and RAR-related orphan receptor gamma T (RORγt) mRNA levels at 24 hours (P =0.004) and at 48 hours (P =0.006) were lower in those receiving a blood transfusion over the first 24 hours postoperatively. The TNFα/IL-10 mRNA ratio at 24 hours (P =0.0006) and at 48 hours (P =0.01) was lower in patients receiving blood transfusion over this period (Figure 2A-H).Figure 2

Bottom Line: One hundred and nineteen patients were recruited.Multivariable analysis confirmed that these observations were independent of the severity of the surgical insult.A mechanistic link is suggested but not proven.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: 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.

Show MeSH
Related in: MedlinePlus