基于诱导痰液样本的基因表达谱，定义哮喘的转录表型
2011/03/28
摘要
背景：前期研究基于哮喘的一些临床指标和人口统计学数据及痰液的细胞计数，对哮喘的临床表型和炎症表型进行了探讨。但对于哮喘转录表型尚未见报道。
目的：通过对诱导痰液的基因表达谱进行分析，在转录水平研究哮喘表型。
方法：收集59名平均年龄为58岁的哮喘患者的诱导痰液样本，这些患者的FEV1为76%预测值。其中有69%的患者采用糖皮质激素吸入治疗。同时对13名健康对照者进行评价。对痰液进行炎症细胞计数，对某些痰液提取RNA，检测转录表达谱，采用GeneSpring GX11进行分析。
结果：对哮喘患者痰液基因表达谱的无监督分层聚类分析显示，能将这些患者分为3组。第一个转录表型组(n = 21)患者具有较低的FEV1预测值，较高的哮喘控制问卷评分，较高的呼出气一氧化氮水平和较高的痰液嗜酸性粒细胞。与第三个转录表型组(n = 24)患者相比，第二个转录表型组(n = 14)患者，具有较低的FEV1预测值和较低的FVC预测值，较高的痰液嗜酸性粒细胞水平。而第三组患者具有较高的痰液巨噬细胞水平，类似于健康对照。哮喘不同转录表型组之间差异性表达基因与炎症反应和免疫反应相关。哮喘患者的IL-1、 TNF-α/NF-κB通路相关基因存在过表达，而且与哮喘患者的临床指标和中性粒细胞气道炎症相关。
结论：基因表达谱为研究哮喘表型的分子机制和分类提供了一个新方法。通过表达谱分析，可以将哮喘分为3个转录表型，这些表型均与临床参数和炎症参数相关。
（陈欣 审校）
J Allergy Clin Immunol. 2011 Jan;127(1):153-60, 160.e1-9.
Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples.
Baines KJ, Simpson JL, Wood LG, Scott RJ, Gibson PG.
Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia. katherine.baines@newcastle.edu.au
Abstract
BACKGROUND: Previous studies have identified clinical or inflammatory phenotypes of asthma on the basis of clinical and demographic parameters or sputum cell counts; however, few studies have defined transcriptional phenotypes of asthma.
OBJECTIVE: To investigate asthma phenotypes at a transcriptional level by using gene expression profiling of induced sputum.
METHODS: Induced sputum samples were collected from 59 people with asthma with a mean age of 58 years and an FEV(1)% predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11.
RESULTS: Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV(1)% predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV(1)% predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation.
CONCLUSION: Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.
J Allergy Clin Immunol. 2011 Jan;127(1):153-60, 160.e1-9.
背景：前期研究基于哮喘的一些临床指标和人口统计学数据及痰液的细胞计数，对哮喘的临床表型和炎症表型进行了探讨。但对于哮喘转录表型尚未见报道。
目的：通过对诱导痰液的基因表达谱进行分析，在转录水平研究哮喘表型。
方法：收集59名平均年龄为58岁的哮喘患者的诱导痰液样本，这些患者的FEV1为76%预测值。其中有69%的患者采用糖皮质激素吸入治疗。同时对13名健康对照者进行评价。对痰液进行炎症细胞计数，对某些痰液提取RNA，检测转录表达谱，采用GeneSpring GX11进行分析。
结果：对哮喘患者痰液基因表达谱的无监督分层聚类分析显示，能将这些患者分为3组。第一个转录表型组(n = 21)患者具有较低的FEV1预测值，较高的哮喘控制问卷评分，较高的呼出气一氧化氮水平和较高的痰液嗜酸性粒细胞。与第三个转录表型组(n = 24)患者相比，第二个转录表型组(n = 14)患者，具有较低的FEV1预测值和较低的FVC预测值，较高的痰液嗜酸性粒细胞水平。而第三组患者具有较高的痰液巨噬细胞水平，类似于健康对照。哮喘不同转录表型组之间差异性表达基因与炎症反应和免疫反应相关。哮喘患者的IL-1、 TNF-α/NF-κB通路相关基因存在过表达，而且与哮喘患者的临床指标和中性粒细胞气道炎症相关。
结论：基因表达谱为研究哮喘表型的分子机制和分类提供了一个新方法。通过表达谱分析，可以将哮喘分为3个转录表型，这些表型均与临床参数和炎症参数相关。
（陈欣 审校）
J Allergy Clin Immunol. 2011 Jan;127(1):153-60, 160.e1-9.
Transcriptional phenotypes of asthma defined by gene expression profiling of induced sputum samples.
Baines KJ, Simpson JL, Wood LG, Scott RJ, Gibson PG.
Centre for Asthma and Respiratory Diseases, Hunter Medical Research Institute, University of Newcastle, Callaghan, Australia. katherine.baines@newcastle.edu.au
Abstract
BACKGROUND: Previous studies have identified clinical or inflammatory phenotypes of asthma on the basis of clinical and demographic parameters or sputum cell counts; however, few studies have defined transcriptional phenotypes of asthma.
OBJECTIVE: To investigate asthma phenotypes at a transcriptional level by using gene expression profiling of induced sputum.
METHODS: Induced sputum samples were collected from 59 people with asthma with a mean age of 58 years and an FEV(1)% predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11.
RESULTS: Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV(1)% predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV(1)% predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation.
CONCLUSION: Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.
J Allergy Clin Immunol. 2011 Jan;127(1):153-60, 160.e1-9.
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在哮喘未达到最佳控制的患者中的气道微生物群和支气管高反应性
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戊糖素在哮喘患者年龄相关和疾病相关的肺功能损伤中的作用
