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

• Published in: Journal of allergy and clinical immunology Vol. 144; no. 5; pp. 1198 - 1213
• Main Authors: Schofield, James P.R., Ward, Jonathan, Montuschi, Paolo, Auffray, Charles, Adcock, Ian M., Howarth, Peter, Vaarala, Outi, Bates, S., Bigler, J., Boedigheimer, M.J., Bønnelykke, K., Bucchioni, E., Burg, D., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., Fichtner, K., Fitch, N., Fowler, S.J., Frey, U., Gahlemann, M., Hashimoto, S., Hedlin, G., Knox, A.J., Lutter, R., Middelveld, R.J.M., Mores, N., Myles, D., Pavlidis, S., Rao, M. Puig N., Rowe, A., Sandström, T., Sigmund, R., Singer, F., Sousa, A.R., Sun, K., Thornton, B., van Aalderen, W.M., Vestbo, J., Wilson, S.J., Badorrek, P., Barber, Clair, Batuwitage, Manohara Kanangana, Berton, A., Bochenek, Grazyna, Dahlén, B., De Alba, Jorge, Dekker, Tamara, Dennison, P., Dodson, Paul, Edwards, Jessica, Emma, Rosalia, Flood, Breda, Guillmant-Farry, E., Hewitt, Lorraine, Hu, X., Johnson, K., Klüglich, M., Kots, Maxim, Kuo, Scott, Lambrecht, Bart, Lantz, A.-S., Latzin, P., Lemonnier, N., Lone-Latif, Saeeda, Manta, Alexander, Martin, Jane, Metcalf, Leanne, Mikus, Maria, Monk, Philip, Nething, K., Nicholas, Ben, Niven, R., Nordlund, B., Nsubuga, S., Palkonen, Susanna, Pellet, J., Pennazza, Giorgio, Petrén, Anne, Pink, Sandy, Rahman-Amin, Malayka, Reynolds, Leanne, Robberechts, Martine, Russell, Kirsty, Rutgers, Michael, Santini, G., Saqi, M., Scott, S., Smith, Katherine M., Stephan, S., Strandberg, K., Szentkereszty, M., Tariq, K., Thorsen, Jonathan, van Drunen, C.M., Wetzel, Kristiane, Wiegman, Coen, Yeyasingham, Elizabeth, Zetterquist, W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2019; Elsevier Limited
• Subjects: Antimicrobial agents; Asthma; Biological products; Biomarkers; Biopsy; bronchial biopsies; bronchial brushings; Cell activation; Clinical trials; Cytokines; Datasets; Epithelial cells; Gene expression; Genomes; IL-17; Inflammatory bowel diseases; Inflammatory diseases; Inflammatory response; Interleukin 1; Interleukin 13; Interleukin 17; Interleukin 6; Interleukin 8; Intestine; Lymphocytes; Medicin och hälsovetenskap; Microbiota; Mucosa; Neutrophilia; Neutrophils; Phenotypes; Phenotyping; Psoriasis; Respiratory diseases; Software; Sputum; Urine; BC; Feno; bronchial brushings; biomarkers; DEG; U-BIOPRED; asthma; DPP4; TDA; bronchial biopsies; psoriasis; IL-17; ICS; IPA; NGS
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2019.03.027

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. We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. 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. 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. 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. [Display omitted]