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IL-17-high asthma with features of a psoriasis immunophenotype
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2019 (Engelska)Ingår i: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 144, nr 5, s. 1198-1213Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

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 IL1BIL6IL8, 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2019. Vol. 144, nr 5, s. 1198-1213
Nyckelord [en]
IL-17, asthma, bronchial biopsies, bronchial brushings, biomarkers, psoriasis
Nationell ämneskategori
Lungmedicin och allergi
Identifikatorer
URN: urn:nbn:se:umu:diva-165356DOI: 10.1016/j.jaci.2019.03.027ISI: 000495004700013PubMedID: 30998987Scopus ID: 2-s2.0-85065197283OAI: oai:DiVA.org:umu-165356DiVA, id: diva2:1372608
Tillgänglig från: 2019-11-25 Skapad: 2019-11-25 Senast uppdaterad: 2023-03-23Bibliografiskt granskad

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Sandström, Thomas

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