Dept of Intensive Care Medicine, Nepean Hospital, Sydney, Australia
Westmead Institute for Medical Research, Centre for Immunology and Allergy Research, Sydney, Australia.
Eur Respir J. 2017 Jun 15;49(6). doi: 10.1183/13993003.02098-2016. Print 2017 Jun.
Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with experiments using well-established infection models.We identified a single-gene biomarker, , which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. studies showed that was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. studies confirmed that was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections. represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.
宿主反应生物标志物可准确地区分流感和细菌感染。然而,已发表的生物标志物需要测量许多基因,因此难以在临床实践中实施。本研究旨在鉴定一种具有与多基因生物标志物相当的高诊断准确性的单基因生物标志物。
在这项研究中,我们结合了对 1071 个人的综合基因组分析和使用成熟感染模型的实验。我们鉴定了一个单基因生物标志物 ,其具有与多基因生物标志物相当的高预测准确性(91%)。 研究表明,TLR7 在浆细胞样树突状细胞中上调 ,浆细胞样树突状细胞是对流感病毒而不是细菌作出反应的抗原呈递细胞。 研究证实, 在流感患者中表达,但在细菌感染中不表达,在多个患者队列(n=521)中得到证实。在一项针对表现为未分化呼吸道疾病的患者(病因包括病毒、细菌和非传染性疾病)的大型前瞻性研究(n=439)中, 在区分流感和细菌感染方面, 显示出 88%的诊断准确性(AUC)和 90%的特异性。 代表在克服基因组检测在临床环境中的转化障碍方面迈出了重要一步;其实施可能会改善呼吸道感染的诊断和管理。