IL-17-high asthma with features of a psoriasis immunophenotype

Abstract

BACKGROUND: The role of interleukin-17 immunity is well established in inflammatory diseases like psoriasis and inflammatory bowel disease but not in asthma where further study is required. OBJECTIVE: To undertake a deep-phenotyping study of asthmatics with up-regulated interleukin-17 immunity. METHODS: Whole genome transcriptomic analysis was performed using epithelial brushings, bronchial biopsies (91 asthmatics patients and 46 healthy controls) and whole blood samples (n=498) from the U-BIOPRED cohort. Gene signatures induced in vitro by interleukin-17 and interleukin-13 in bronchial epithelial cells were used to identify patients with interleukin-17-high and interleukin-13-high phenotypes of asthma. RESULTS: 22 out of 91 patients were identified with interleukin-17 and 9 patients with interleukin-13 gene signatures. The interleukin-17-high asthmatics were characterised 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 interleukin-17-high patients were shared with those reported as altered in psoriasis lesions, and included genes regulating epithelial barrier function and defence mechanisms, such as interleukin-1β, interleukin-6, interleukin-8, and beta-defensin. CONCLUSION: The interleukin-17-high asthma phenotype, characterized by bronchial epithelial dysfunction, upregulated anti-microbial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway which should be considered as a biomarker for this phenotype in further studies, including clinical trials targeting interleukin-17.