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

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 leuk...

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Autores principales: Fragkou, Paraskevi C, Torrance, Hew D, Pearse, Rupert M, Ackland, Gareth L, Prowle, John R, Owen, Helen C, Hinds, Charles J, O’Dwyer, Michael J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201915/
https://www.ncbi.nlm.nih.gov/pubmed/25270110
http://dx.doi.org/10.1186/s13054-014-0541-x
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author Fragkou, Paraskevi C
Torrance, Hew D
Pearse, Rupert M
Ackland, Gareth L
Prowle, John R
Owen, Helen C
Hinds, Charles J
O’Dwyer, Michael J
author_facet Fragkou, Paraskevi C
Torrance, Hew D
Pearse, Rupert M
Ackland, Gareth L
Prowle, John R
Owen, Helen C
Hinds, Charles J
O’Dwyer, Michael J
author_sort Fragkou, Paraskevi C
collection PubMed
description 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 (T(h)1) and T helper cell type 17 (T(h)17) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-014-0541-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-42019152014-10-20 Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study Fragkou, Paraskevi C Torrance, Hew D Pearse, Rupert M Ackland, Gareth L Prowle, John R Owen, Helen C Hinds, Charles J O’Dwyer, Michael J Crit Care Research 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 (T(h)1) and T helper cell type 17 (T(h)17) 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13054-014-0541-x) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-01 2014 /pmc/articles/PMC4201915/ /pubmed/25270110 http://dx.doi.org/10.1186/s13054-014-0541-x Text en © Fragkou et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Fragkou, Paraskevi C
Torrance, Hew D
Pearse, Rupert M
Ackland, Gareth L
Prowle, John R
Owen, Helen C
Hinds, Charles J
O’Dwyer, Michael J
Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
title Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
title_full Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
title_fullStr Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
title_full_unstemmed Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
title_short Perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
title_sort perioperative blood transfusion is associated with a gene transcription profile characteristic of immunosuppression: a prospective cohort study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4201915/
https://www.ncbi.nlm.nih.gov/pubmed/25270110
http://dx.doi.org/10.1186/s13054-014-0541-x
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