Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.
Cluster analysis of sputum cytokine-high profiles reveals diversity in T(h)2-high asthma patients.
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DOI：
10.1186/s12931-017-0524-y
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发表时间：
2017-02-23
影响因子：
5.8
通讯作者：
Bullens DM
中科院分区：
文献类型：
--
作者：
Seys SF;Scheers H;Van den Brande P;Marijsse G;Dilissen E;Van Den Bergh A;Goeminne PC;Hellings PW;Ceuppens JL;Dupont LJ;Bullens DM
哮喘的特点是异质性炎症，可细分为T(H)2-高和T(H)2-低气道炎症。在大量未选择的患者队列中缺乏对更广泛的呼吸道细胞因子的分析。患者(n = 205)如果某一特定细胞因子的表达超出对照组(n = 80)相应的第10/90百分位范围，则被定义为“细胞因子低/高”。根据痰细胞因子图谱，使用非监督的层次聚类来确定聚类。半数患者(n = 108；52.6%)具有典型的T(H)2高(“IL-4、IL-5和/或IL-13高”)痰细胞因子谱。非监督聚类分析显示有5个聚类群。具有“IL-4和/或IL-13高”模式的患者令人惊讶地没有集群，而是平均分布在5个集群中。IL-5-、IL-17A-/F-和IL-25-高的患者被限制在第1组(n = 24)，在基线和2年后，痰中嗜酸性粒细胞和中性粒细胞计数增加，肺功能参数变差。另外还鉴定了4个簇：“IL-5-高或IL-10-高”(n = 16)，“IL-6-高”(n = 8)，“IL-22-高”(n = 25)。第5组(n = 132)包括无高细胞因子模式的患者或仅有高IL-4和/或IL-13模式的患者。我们通过生物聚类法鉴定了5种独特的哮喘分子表型。在5个簇中，有4个是2型细胞因子与非2型细胞因子聚集。因此，非监督分析不支持先验类型2与非类型2分子表型。Www.Clinicaltrials.gov NCT01224938。已于2010年10月18日注册。本文的在线版本(doi：10.1186/s12931-0170524-y)包含补充材料，授权用户可以使用。
Asthma is characterized by a heterogeneous inflammatory profile and can be subdivided into T(h)2-high and T(h)2-low airway inflammation. Profiling of a broader panel of airway cytokines in large unselected patient cohorts is lacking. Patients (n = 205) were defined as being “cytokine-low/high” if sputum mRNA expression of a particular cytokine was outside the respective 10th/90th percentile range of the control group (n = 80). Unsupervised hierarchical clustering was used to determine clusters based on sputum cytokine profiles. Half of patients (n = 108; 52.6%) had a classical T(h)2-high (“IL-4-, IL-5- and/or IL-13-high”) sputum cytokine profile. Unsupervised cluster analysis revealed 5 clusters. Patients with an “IL-4- and/or IL-13-high” pattern surprisingly did not cluster but were equally distributed among the 5 clusters. Patients with an “IL-5-, IL-17A-/F- and IL-25- high” profile were restricted to cluster 1 (n = 24) with increased sputum eosinophil as well as neutrophil counts and poor lung function parameters at baseline and 2 years later. Four other clusters were identified: “IL-5-high or IL-10-high” (n = 16), “IL-6-high” (n = 8), “IL-22-high” (n = 25). Cluster 5 (n = 132) consists of patients without “cytokine-high” pattern or patients with only high IL-4 and/or IL-13. We identified 5 unique asthma molecular phenotypes by biological clustering. Type 2 cytokines cluster with non-type 2 cytokines in 4 out of 5 clusters. Unsupervised analysis thus not supports a priori type 2 versus non-type 2 molecular phenotypes. www.clinicaltrials.gov NCT01224938. Registered 18 October 2010. The online version of this article (doi:10.1186/s12931-017-0524-y) contains supplementary material, which is available to authorized users.