① 先前有研究定义了成人哮喘的转录子亚型，然而这并不容易应用于临床，尤其是儿童哮喘；② 应用Illumina芯片技术检测133例哮喘患儿和11例健康对照的PBMC基因表达情况；③采用了2048个基因的k-means聚类算法将哮喘患儿分组；④ 84基因特征可以识别儿童重症哮喘的白细胞，以及成人重症哮喘的CD8+T细胞；⑤ PBMC和CD8+T细胞可作为重症哮喘研究和鉴别的重要靶点
Clinical & Experimental Allergy
Genetic Profiles of Transcriptomic Clusters of Childhood Asthma Determine Specific Severe Subtype
Background: Previous studies have defined transcriptomic subtypes of adult asthma using samples of induced sputum and bronchial epithelium; however, those procedures are not readily applicable in the clinic,especially for childhood asthma.
Methods: Gene expression of PBMC from 133 asthmatic children and 11 healthy controls was measured with Illumina microarrays. We applied the k-means clustering algorithm of 2048 genes to assign asthmatic children into clusters. Genes with differential expression between asthma clusters and healthy controls were used to investigate whether they could identify severe asthma of children and adults.
Results: We identified three asthma clusters with distinct inflammatory profiles in peripheral blood. Cluster 1 had the highest eosinophil count. Cluster 2 showed lower counts of both eosinophils and neutrophils.Cluster 3 had the highest neutrophil count, and the poorest treatment control. Compared with other patients, Cluster 3 exhibited a unique gene expression pattern which was associated with changes in the glucocorticoid signaling and activation of the T helper 1/T helper 17 (TH1/TH17) immune pathways. In the validation studies, an 84-gene signature could identify severe asthma in children on leukocytes, as well as severe asthma in adults on CD8+ T cells.
Conclusions: Gene expression profiling of PBMC is useful for the identification of TH1/TH17-mediated asthma with poor treatment control. PBMC and CD8+ T cells could be important targets for the investigation and identification of severe asthma.
Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University
Y.-L. Yeh, M.-W. Su, B.-L. Chiang, Y.-H. Yang, C.-H. Tsai, Y. L. Lee