A Transcriptomic Approach to Understand Patient Susceptibility to Pneumonia After Abdominal Surgery.

Autor:	Torrance HD; Division of Anaesthetics, Pain Medicine & Intensive Care Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London. UK., Zhang P; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK.; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK., Longbottom ER; Centre for Translational Medicine & Therapeutics, William Harvey Institute, Faculty of Medicine & Dentistry at Queen Mary University of London, London. UK., Mi Y; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK., Whalley JP; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK.; Center for Cancer Cell Biology, Immunology, and Infection, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL., Allcock A; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK., Kwok AJ; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK., Cano-Gamez E; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK., Geoghegan CG; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK., Burnham KL; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK., Antcliffe DB; Division of Anaesthetics, Pain Medicine & Intensive Care Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London. UK., Davenport EE; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK., Pearse RM; Centre for Translational Medicine & Therapeutics, William Harvey Institute, Faculty of Medicine & Dentistry at Queen Mary University of London, London. UK., O'Dwyer MJ; Department of Anaesthesia and Critical Care, St Vincent's University Hospital, Dublin. Ireland., Hinds CJ; Centre for Translational Medicine & Therapeutics, William Harvey Institute, Faculty of Medicine & Dentistry at Queen Mary University of London, London. UK., Knight JC; Wellcome Centre for Human Genetics, University of Oxford, Oxford. UK.; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK., Gordon AC; Division of Anaesthetics, Pain Medicine & Intensive Care Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, London. UK.
Jazyk:	angličtina
Zdroj:	Annals of surgery [Ann Surg] 2024 Mar 01; Vol. 279 (3), pp. 510-520. Date of Electronic Publication: 2023 Jul 27.
DOI:	10.1097/SLA.0000000000006050
Abstrakt:	Objective: To describe immune pathways and gene networks altered following major abdominal surgery and to identify transcriptomic patterns associated with postoperative pneumonia. Background: Nosocomial infections are a major healthcare challenge, developing in over 20% of patients aged 45 or over undergoing major abdominal surgery, with postoperative pneumonia associated with an almost 5-fold increase in 30-day mortality. Methods: From a prospective consecutive cohort (n=150) undergoing major abdominal surgery, whole-blood RNA was collected preoperatively and at 3 time-points postoperatively (2-6, 24, and 48 h). Twelve patients diagnosed with postoperative pneumonia and 27 matched patients remaining infection-free were identified for analysis with RNA-sequencing. Results: Compared to preoperative sampling, 3639 genes were upregulated and 5043 downregulated at 2 to 6 hours. Pathway analysis demonstrated innate-immune activation with neutrophil degranulation and Toll-like-receptor signaling upregulation alongside adaptive-immune suppression. Cell-type deconvolution of preoperative RNA-sequencing revealed elevated S100A8/9-high neutrophils alongside reduced naïve CD4 T-cells in those later developing pneumonia. Preoperatively, a gene-signature characteristic of neutrophil degranulation was associated with postoperative pneumonia acquisition ( P =0.00092). A previously reported Sepsis Response Signature (SRSq) score, reflecting neutrophil dysfunction and a more dysregulated host response, at 48 hours postoperatively, differed between patients subsequently developing pneumonia and those remaining infection-free ( P =0.045). Analysis of the novel neutrophil gene-signature and SRSq scores in independent major abdominal surgery and polytrauma cohorts indicated good predictive performance in identifying patients suffering later infection. Conclusions: Major abdominal surgery acutely upregulates innate-immune pathways while simultaneously suppressing adaptive-immune pathways. This is more prominent in patients developing postoperative pneumonia. Preoperative transcriptomic signatures characteristic of neutrophil degranulation and postoperative SRSq scores may be useful predictors of subsequent pneumonia risk. Competing Interests: R.M.P. declares research grants and/or honoraria from Edwards Lifesciences, Intersurgical and GlaxoSmithkline and A.C.G. declares consulting fees from AstraZeneca, both unrelated to this project. The remaining authors report no conflict of interest. (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)
Databáze:	MEDLINE
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