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

Östling, Jörgen; van Geest, Marleen; Schofield, James P R; Jevnikar, Zala; Wilson, Susan; Ward, Jonathan; Lutter, Rene; Shaw, Dominick E; Bakke, Per S; Caruso, Massimo; Dahlen, Sven-Erik; Fowler, Stephen J; Horváth, Ildikó; Krug, Norbert; Montuschi, Paolo; Sanak, Marek; Sandström, Thomas; Sun, Kai; Pandis, Ioannis; Auffray, Charles; ... (2019). IL-17-high asthma with features of a psoriasis immunophenotype. Journal of allergy and clinical immunology, 144(5), pp. 1198-1213. Elsevier 10.1016/j.jaci.2019.03.027

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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 β-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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
Subjects:	600 Technology > 610 Medicine & health
ISSN:	1097-6825
Publisher:	Elsevier
Language:	English
Submitter:	Anette van Dorland
Date Deposited:	13 Jan 2020 08:11
Last Modified:	20 Jul 2022 10:01
Publisher DOI:	10.1016/j.jaci.2019.03.027
PubMed ID:	30998987
Additional Information:	Publication of the U-BIOPRED Study group, with the following Uni-Be members explicitly mentioned as Contributors: Carmen Casaulta, Philip Latzin, Florian Singer
Uncontrolled Keywords:	IL-17 asthma biomarkers bronchial biopsies bronchial brushings psoriasis
URI:	https://boris.unibe.ch/id/eprint/138344