Mariani Thomas J, Qiu Xing, Chu ChinYi, Wang Lu, Thakar Juilee, Holden-Wiltse Jeanne, Corbett Anthony, Topham David J, Falsey Ann R, Caserta Mary T, Walsh Edward E
Division of Neonatology and Pediatric Molecular and Personalized Medicine Program.
Department of Medicine, University of Rochester Medical Center.
J Infect Dis. 2017 Nov 15;216(8):1027-1037. doi: 10.1093/infdis/jix400.
Nearly all children are infected with respiratory syncytial virus (RSV) within the first 2 years of life, with a minority developing severe disease (1%-3% hospitalized). We hypothesized that an assessment of the adaptive immune system, using CD4+ T-lymphocyte transcriptomics, would identify gene expression correlates of disease severity.
Infants infected with RSV representing extremes of clinical severity were studied. Mild illness (n = 23) was defined as a respiratory rate (RR) < 55 and room air oxygen saturation (SaO2) ≥ 97%, and severe illness (n = 23) was defined as RR ≥ 65 and SaO2 ≤ 92%. RNA from fresh, sort-purified CD4+ T cells was assessed by RNA sequencing.
Gestational age, age at illness onset, exposure to environmental tobacco smoke, bacterial colonization, and breastfeeding were associated (adjusted P < .05) with disease severity. RNA sequencing analysis reliably measured approximately 60% of the genome. Severity of RSV illness had the greatest effect size upon CD4 T-cell gene expression. Pathway analysis identified correlates of severity, including JAK/STAT, prolactin, and interleukin 9 signaling. We also identified genes and pathways associated with timing of symptoms and RSV group (A/B).
These data suggest fundamental changes in adaptive immune cell phenotypes may be associated with RSV clinical severity.
几乎所有儿童在生命的头两年内都会感染呼吸道合胞病毒（RSV），少数儿童会发展为严重疾病（1%-3%住院）。我们假设，使用CD4+T淋巴细胞转录组学对适应性免疫系统进行评估，将能够识别出与疾病严重程度相关的基因表达。
对感染RSV且临床表现严重程度差异极大的婴儿进行研究。轻度疾病（n = 23）定义为呼吸频率（RR）< 55且室内空气氧饱和度（SaO2）≥ 97%，重度疾病（n = 23）定义为RR≥ 65且SaO2≤ 92%。通过RNA测序评估新鲜的、分选纯化的CD4+T细胞中的RNA。
胎龄、发病年龄（age at illness onset）、接触环境烟草烟雾、细菌定植和母乳喂养与疾病严重程度相关（校正P < 0.05）。RNA测序分析可靠地检测了约60%的基因组。RSV疾病的严重程度对CD4 T细胞基因表达的影响最大。通路分析确定了与严重程度相关的因素，包括JAK/STAT、催乳素和白细胞介素9信号传导。我们还确定了与症状出现时间和RSV组（A/B）相关的基因和通路。
这些数据表明适应性免疫细胞表型的根本变化可能与RSV临床严重程度相关。
