IL-17-high asthma with features of a psoriasis immunophenotype
IL-17-high asthma with features of a psoriasis immunophenotype
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DOI：
10.1016/j.jaci.2019.03.027
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发表时间：
2019-11-01
影响因子：
14.2
通讯作者：
Wilson, S. J.
中科院分区：
文献类型：
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作者：
Oestling, Joergen;van Geest, Marleen;Wilson, S. J.
背景资料：IL-17免疫的作用在炎症性疾病如银屑病和炎症性肠病患者中得到了很好的确立，但在哮喘患者中没有，需要进一步研究。目的：我们试图对IL-17免疫上调的哮喘患者进行深入的表型研究。通过使用上皮刷检、支气管活检标本进行全基因组转录组学分析（91名哮喘患者和46名健康对照受试者），以及来自用于预测呼吸系统疾病结局的无偏生物标志物（U-BIOPRED）队列的全血样本（n = 498）。结果：91例哮喘患者中22例为IL-17阳性，9例为IL-13阳性。IL-17高水平哮喘患者的特征为频繁急性发作风险、气道（痰液和粘膜）嗜酸性粒细胞增多、肺微生物群多样性降低和血栓烷B2途径激活的尿生物标志物证据。在通路分析中，IL-17高水平哮喘患者的差异表达基因与银屑病病变中报道的改变的基因是相同的，包括调节上皮屏障功能和防御机制的基因，如IL 1B、IL 6、IL 8和β-防御素。IL-17高哮喘表型的特征是支气管上皮功能障碍以及抗菌和炎症反应上调，类似于银屑病的免疫表型，包括血栓烷B2途径的激活，在进一步的研究中，包括靶向IL-17的临床试验，应将其视为该表型的生物标志物。
Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required.Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity.Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17-high and IL-13-high asthma phenotypes.Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17-high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and beta-defensin.Conclusion: The IL-17-high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.