Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
Clin Exp Allergy. 2018 Sep;48(9):1164-1172. doi: 10.1111/cea.13175. Epub 2018 Jun 5.
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.
We aim to dissect the transcriptomic clusters of childhood asthma using highly variably expressed genes of peripheral blood mononuclear cells (PBMC) among patients.
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.
We identified 3 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 signalling and activation of the T helper 1/T helper 17 (T 1/T 17) immune pathways. In the validation studies, an 84-gene signature could identify severe asthma in children on leucocytes, as well as severe asthma in adults on CD8 T cells.
Gene expression profiling of PBMC is useful for the identification of T 1/T 17-mediated asthma with poor treatment control. PBMC and CD8 T cells could be important targets for the investigation and identification of severe asthma.
先前的研究使用诱导痰和支气管上皮样本定义了成人哮喘的转录组亚型；然而，这些程序在临床上不容易实施，尤其是对于儿童哮喘。
我们旨在通过患者外周血单核细胞（PBMC）中高度可变表达的基因来剖析儿童哮喘的转录组簇。
使用 Illumina 微阵列测量了 133 名哮喘儿童和 11 名健康对照者的 PBMC 基因表达。我们应用了 2048 个基因的 k-均值聚类算法将哮喘儿童分配到聚类中。使用在哮喘簇和健康对照组之间差异表达的基因来研究它们是否可以识别儿童和成人的严重哮喘。
我们在外周血中确定了 3 个具有不同炎症特征的哮喘簇。簇 1 具有最高的嗜酸性粒细胞计数。簇 2 显示嗜酸性粒细胞和中性粒细胞计数均较低。簇 3 具有最高的中性粒细胞计数和最差的治疗控制效果。与其他患者相比，簇 3 表现出独特的基因表达模式，与糖皮质激素信号通路和辅助性 T 细胞 1/辅助性 T 细胞 17（T1/T17）免疫途径的激活变化有关。在验证研究中，一个 84 基因特征可以在白细胞上识别儿童的严重哮喘，也可以在 CD8 T 细胞上识别成人的严重哮喘。
PBMC 的基因表达谱对于鉴定治疗控制效果差的 T1/T17 介导的哮喘很有用。PBMC 和 CD8 T 细胞可能是研究和识别严重哮喘的重要靶点。
