Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection.
Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection.
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DOI：
10.1371/journal.pone.0131927
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Staal FJ
中科院分区：
文献类型：
--
作者：
Brand HK;Ahout IM;de Ridder D;van Diepen A;Li Y;Zaalberg M;Andeweg A;Roeleveld N;de Groot R;Warris A;Hermans PW;Ferwerda G;Staal FJ
幼儿呼吸道病毒感染的临床过程不可预测，从普通感冒到呼吸衰竭。从轻度疾病到重度疾病的转变发生得很快且难以预测。疾病严重程度背后的病理生理学仍然难以捉摸。迫切需要更好地了解这种疾病的免疫反应，以找到有助于临床决策的生物标志物。在一项前瞻性研究中，对 26 名被诊断患有严重、中度或轻度呼吸道合胞病毒 (RSV) 感染的儿童的血液样本进行了流式细胞术和全基因组基因表达分析。在连续三个冬季的第二组 80 名儿童中，使用 Q-PCR 验证了差异表达基因。还对第二队列和第一队列中重症病例的恢复样本进行了 FACS 分析。严重 RSV 感染与外周血中 CD4+ T、CD8+ T 和 NK 细胞短暂但显着的减少有关。两个队列中的基因表达分析均确定 Olfactomedin4 (OLFM4) 是轻度和重度 RSV 感染儿童之间的完全区分标记，PAM 交叉验证误差为 0%。在校正住院年龄和胎龄后，OLFM4 基因表达水平高于 -7.5 的患者患严重疾病的可能性是其他患者的 6 倍。通过将血细胞亚群的全基因组表达谱与临床注释良好的样本相结合，OLFM4 被确定为儿童 RSV 感染严重程度的生物标志物。
Respiratory viral infections follow an unpredictable clinical course in young children ranging from a common cold to respiratory failure. The transition from mild to severe disease occurs rapidly and is difficult to predict. The pathophysiology underlying disease severity has remained elusive. There is an urgent need to better understand the immune response in this disease to come up with biomarkers that may aid clinical decision making. In a prospective study, flow cytometric and genome-wide gene expression analyses were performed on blood samples of 26 children with a diagnosis of severe, moderate or mild Respiratory Syncytial Virus (RSV) infection. Differentially expressed genes were validated using Q-PCR in a second cohort of 80 children during three consecutive winter seasons. FACS analyses were also performed in the second cohort and on recovery samples of severe cases in the first cohort. Severe RSV infection was associated with a transient but marked decrease in CD4+ T, CD8+ T, and NK cells in peripheral blood. Gene expression analyses in both cohorts identified Olfactomedin4 (OLFM4) as a fully discriminative marker between children with mild and severe RSV infection, giving a PAM cross-validation error of 0%. Patients with an OLFM4 gene expression level above -7.5 were 6 times more likely to develop severe disease, after correction for age at hospitalization and gestational age. By combining genome-wide expression profiling of blood cell subsets with clinically well-annotated samples, OLFM4 was identified as a biomarker for severity of pediatric RSV infection.
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