Haeusler Gabrielle M, Garnham Alexandra L, Li-Wai-Suen 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
Department of Infectious Diseases Peter MacCallum Cancer Centre Melbourne VIC Australia.
NHMRC National Centre for Infections in Cancer Sir Peter MacCallum Department of Oncology University of Melbourne Melbourne VIC Australia.
Clin Transl Immunology. 2022 May 17;11(5):e1383. doi: 10.1002/cti2.1383. eCollection 2022.
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.
Whole-genome transcriptional profiling was conducted on PBMCs collected during episodes of FN in children with cancer at presentation to the hospital (Day 1; = 73) and within 8-24 h (Day 2; = 28) after admission. Differentially expressed genes as well as gene pathways that correlated with clinical outcomes were defined for different infectious outcomes.
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.
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.
发热性中性粒细胞减少症（FN）是儿童癌症患者治疗中断和意外住院的主要原因。本研究调查了患有癌症和FN的儿童外周血单个核细胞（PBMC）的转录组，以确定严重感染的潜在预测指标。
对癌症患儿在入院时（第1天；n = 73）以及入院后8 - 24小时内（第2天；n = 28）FN发作期间采集的PBMC进行全基因组转录谱分析。针对不同的感染结局，定义了与临床结局相关的差异表达基因以及基因通路。
与无感染记录的发作相比，在入院时发现了FN患儿且有感染记录的患儿中与特定免疫反应相关的基因表达的整体差异。这些差异在随后的8 - 24小时内消失。在入院时和第2天都发现了菌血症特有的不同基因特征。还观察到菌血症发作与细菌感染、病毒感染和临床定义感染发作之间的基因特征差异。仅发现非血流细菌感染和病毒感染之间基因表达谱的细微差异。
FN发作期间的血液转录组免疫谱分析可能有助于监测，并有助于为癌症患儿不同感染病因确定适当的治疗方法。
