与儿童肺炎微生物病因及疾病严重程度相关的转录组生物标志物

Transcriptomic Biomarkers Associated With Microbiological Etiology and Disease Severity in Childhood Pneumonia.

作者信息

Williams Derek J, Gautam Shruti, Creech C Buddy, Jimenez Natalia, Anderson Evan J, Bosinger Steven E, Grimes Tyler, Arnold Sandra R, McCullers Jonathan A, Goll Johannes, Edwards Kathryn M, Ramilo Octavio

机构信息

Department of Pediatrics, Vanderbilt University School of Medicine and the Monroe Carell Jr Children's Hospital at Vanderbilt University Medical Center, Nashville, Tennessee.

Department of Biomedical Data Science and Bioinformatics, The Emmes Company, LLC, Rockville, Maryland.

出版信息

J Infect Dis. 2025 Feb 20;231(2):e277-e289. doi: 10.1093/infdis/jiae491.

DOI:10.1093/infdis/jiae491

PMID:39397536

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11841634/

Abstract

BACKGROUND

Challenges remain in discerning microbiologic etiology and disease severity in childhood pneumonia. Defining host transcriptomic profiles during illness may facilitate improved diagnostic and prognostic approaches.

METHODS

Using whole blood RNA sequencing from 222 hospitalized children with radiographic pneumonia and 45 age-matched controls, we identified differentially expressed (DE) genes that best identified children according to detected microbial pathogens (viral only vs bacterial only and typical vs atypical bacterial [with or without [±] viral co-detection]) and an ordinal measure of phenotypic severity (moderate, severe, very severe).

RESULTS

Overall, 135 (61%) children had viral-only detections, 15 (7%) had typical bacterial detections (± viral co-detections), and 26 (12%) had atypical bacterial detections (± viral co-detections). Eleven DE genes distinguished between viral-only and bacterial-only detections. Sixteen DE genes distinguished between atypical and typical bacterial detections (± viral co-detections). Nineteen DE genes distinguished between levels of pneumonia severity, including 4 genes also identified in the viral-only versus bacterial-only model (IGHGP, PI3, CD177, RAP1GAP1) and 4 genes from the typical versus atypical bacterial model (PRSS23, IFI27, OLFM4, ABO).

CONCLUSIONS

We identified transcriptomic biomarkers associated with microbial detections and phenotypic severity in children hospitalized with pneumonia. These DE genes are promising candidates for validation and translation into diagnostic and prognostic tools.

摘要

背景

在辨别儿童肺炎的微生物病因和疾病严重程度方面仍存在挑战。确定疾病期间的宿主转录组谱可能有助于改进诊断和预后方法。

方法

我们对222名患有放射性肺炎的住院儿童和45名年龄匹配的对照进行全血RNA测序，根据检测到的微生物病原体（仅病毒感染与仅细菌感染，以及典型与非典型细菌感染[有无[±]病毒共同检测]）和表型严重程度的有序测量（中度、重度、极重度），确定了最能区分儿童的差异表达（DE）基因。

结果

总体而言，135名（61%）儿童仅检测到病毒，15名（7%）检测到典型细菌（±病毒共同检测），26名（12%）检测到非典型细菌（±病毒共同检测）。11个DE基因区分了仅病毒感染和仅细菌感染。16个DE基因区分了非典型和典型细菌感染（±病毒共同检测）。19个DE基因区分了肺炎严重程度级别，其中包括在仅病毒感染与仅细菌感染模型中也鉴定出的4个基因（IGHGP、PI3、CD177、RAP1GAP1）以及典型与非典型细菌模型中的4个基因（PRSS23、IFI27、OLFM4、ABO）。