J�rgen �stling
IL-17–high asthma with features of a psoriasis immunophenotype
?stling, J?rgen; 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.; Horv?th, Ildik?; Krug, Norbert; Montuschi, Paolo; Sanak, Marek; Sandstr?m, Thomas; Sun, Kai; Pandis, Ioannis; Auffray, Charles; Sousa, Ana R.; Guo, Yike; Adcock, Ian M.; Howarth, Peter; Chung, Kian Fan; Bigler, Jeanette; Sterk, Peter J.; Skipp, Paul J.; Djukanovi?, Ratko; Vaarala, Outi; Ahmed, H.; Auffray, C.; Bakke, P.; Bansal, A. T.; Baribaud, F.; Bates, S.; Bel, E. H.; Bigler, J.; Bisgaard, H.; Boedigheimer, M. J.; B?nnelykke, K.; Brandsma, J.; Brinkman, P.; Bucchioni, E.; Burg, D.; Bush, A.; Caruso, M.; Chaiboonchoe, A.; Chanez, P.; Chung, K. F.; Compton, C. H.; Corfield, J.; D'Amico, A.; Dahlen, S. E.; De Meulder, B.; Djukanovic, R.; Erpenbeck, V. J.; Erzen, D.; Fichtner, K.; Fitch, N.; Fleming, L. J.; Formaggio, E.; Fowler, S. J.; Frey, U.; Gahlemann, M.; Geiser, T.; Guo,...
Authors
Marleen van Geest
James P.R. Schofield
Zala Jevnikar
Susan Wilson
Jonathan Ward
Rene Lutter
Dominick E. Shaw
Per S. Bakke
Massimo Caruso
Sven Erik Dahlen
Stephen J. Fowler
Ildik� Horv�th
Norbert Krug
Paolo Montuschi
Marek Sanak
Thomas Sandstr�m
Kai Sun
Ioannis Pandis
Charles Auffray
Ana R. Sousa
Yike Guo
Ian M. Adcock
Peter Howarth
Kian Fan Chung
Jeanette Bigler
Peter J. Sterk
Paul J. Skipp
Ratko Djukanovi?
Outi Vaarala
H. Ahmed
C. Auffray
P. Bakke
A. T. Bansal
F. Baribaud
S. Bates
E. H. Bel
J. Bigler
H. Bisgaard
M. J. Boedigheimer
K. B�nnelykke
J. Brandsma
P. Brinkman
E. Bucchioni
D. Burg
A. Bush
M. Caruso
A. Chaiboonchoe
P. Chanez
K. F. Chung
C. H. Compton
J. Corfield
A. D'Amico
S. E. Dahlen
B. De Meulder
R. Djukanovic
V. J. Erpenbeck
D. Erzen
K. Fichtner
N. Fitch
L. J. Fleming
E. Formaggio
S. J. Fowler
U. Frey
M. Gahlemann
T. Geiser
Y. Guo
S. Hashimoto
J. Haughney
G. Hedlin
P. W. Hekking
T. Higenbottam
J. M. Hohlfeld
C. Holweg
I. Horv�th
P. Howarth
A. J. James
R. Knowles
A. J. Knox
N. Krug
D. Lefaudeux
M. J. Loza
R. Lutter
A. Manta
S. Masefield
A. Mazein
A. Meiser
R. J.M. Middelveld
M. Miralpeix
P. Montuschi
N. Mores
C. S. Murray
J. Musial
D. Myles
L. Pahus
I. Pandis
S. Pavlidis
P. Powell
G. Pratic�
Abstract
© 2019 American Academy of Allergy, Asthma & Immunology 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.
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 18, 2019 |
Online Publication Date | Apr 15, 2019 |
Publication Date | Nov 1, 2019 |
Deposit Date | Aug 25, 2020 |
Journal | Journal of Allergy and Clinical Immunology |
Print ISSN | 0091-6749 |
Electronic ISSN | 1097-6825 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 144 |
Issue | 5 |
Pages | 1198-1213 |
DOI | https://doi.org/10.1016/j.jaci.2019.03.027 |
Public URL | https://nottingham-repository.worktribe.com/output/3113772 |
Publisher URL | https://linkinghub.elsevier.com/retrieve/pii/S0091674919304841 |
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search