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Blood transcriptomics identifies immune signatures indicative of infectious complications in childhood cancer patients with febrile neutropenia
Author(s) -
Haeusler Gabrielle M,
Garnham Alexandra L,
LiWaiSuen Connie SN,
Clark Julia E,
Babl Franz E,
Allaway Zoe,
Slavin Monica A,
Mechinaud Francoise,
Smyth Gordon K,
Phillips Bob,
Thursky Karin A,
Pellegrini Marc,
Doerflinger Marcel
Publication year - 2022
Publication title -
clinical and translational immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.321
H-Index - 34
ISSN - 2050-0068
DOI - 10.1002/cti2.1383
Subject(s) - transcriptome , immune system , neutropenia , immunology , febrile neutropenia , peripheral blood mononuclear cell , medicine , gene expression profiling , gene , cancer , blood cancer , gene expression , biology , chemotherapy , genetics , in vitro
Abstract Objectives Febrile neutropenia (FN) is a major cause of treatment disruption and unplanned hospitalization in childhood cancer patients. This study investigated the transcriptome of peripheral blood mononuclear cells (PBMCs) in children with cancer and FN to identify potential predictors of serious infection. Methods Whole‐genome transcriptional profiling was conducted on PBMCs collected during episodes of FN in children with cancer at presentation to the hospital (Day 1; n  = 73) and within 8–24 h (Day 2; n  = 28) after admission. Differentially expressed genes as well as gene pathways that correlated with clinical outcomes were defined for different infectious outcomes. Results Global differences in gene expression associated with specific immune responses in children with FN and documented infection, compared to episodes without documented infection, were identified at admission. These differences resolved over the subsequent 8–24 h. Distinct gene signatures specific for bacteraemia were identified both at admission and on Day 2. Differences in gene signatures between episodes with bacteraemia and episodes with bacterial infection, viral infection and clinically defined infection were also observed. Only subtle differences in gene expression profiles between non‐bloodstream bacterial and viral infections were identified. Conclusion Blood transcriptome immune profiling analysis during FN episodes may inform monitoring and aid in defining adequate treatment for different infectious aetiologies in children with cancer.

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