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Observational Study
. 2017 Aug;140(2):395-406.
doi: 10.1016/j.jaci.2016.10.034. Epub 2016 Dec 5.

Identification of IL-17F/frequent exacerbator endotype in asthma

Fabio L M Ricciardolo  1 , Valentina Sorbello  2 , Anna Folino  2 , Fabio Gallo  3 , Gian Mario Massaglia  4 , Gabriella Favatà  5 , Salvatore Conticello  5 , Davide Vallese  6 , Federica Gani  4 , Mario Malerba  7 , Gert Folkerts  8 , Giovanni Rolla  9 , Mirella Profita  10 , Thais Mauad  11 , Antonino Di Stefano  6 , Giorgio Ciprandi  12
Affiliations
Free article
Observational Study

Identification of IL-17F/frequent exacerbator endotype in asthma

Fabio L M Ricciardolo et al. J Allergy Clin Immunol. 2017 Aug.
Free article

Abstract

Background: Severe asthma might be associated with overexpression of Th17 cytokines, which induce neutrophil recruitment via neutrophil-mobilizing cytokines in airways.

Objective: To study IL-17-related cytokines in nasal/bronchial biopsies from controls and mild asthmatics (MAs) to severe asthmatics (SAs) in relation to exacerbation rate.

Methods: Inflammatory cells and IL-17A+, IL-17F+, IL-21+, IL-22+, and IL-23+ cells were examined by immunohistochemistry in cryostat sections of bronchial/nasal biopsies obtained from 33 SAs (21 frequent exacerbators [FEs]), 31 MAs (3 FEs), and 14 controls. IL-17F protein was also measured by ELISA in bronchial/nasal lysates and by immunohistochemistry in bronchial tissue obtained from subjects who died because of fatal asthma. Immunofluorescence/confocal microscopy was used for IL-17F colocalization.

Results: Higher number (P < .05) of neutrophils, IL-17A+, IL-17F+, and IL-21+ cells in bronchial biopsies and higher numbers (P < .01) of IL-17F+ and IL-21+ cells in nasal biopsies were observed in SAs compared with MAs. Bronchial IL-17F+ cells correlated with bronchial neutrophils (r = 0.54), exacerbation rate (r = 0.41), and FEV1 (r = -0.46). Nasal IL-17F+ cells correlated with bronchial IL-17F (r = 0.35), exacerbation rate (r = 0.47), and FEV1 (r = -0.61). FEs showed increased number of bronchial neutrophils/eosinophils/CD4+/CD8+ cells and bronchial/nasal IL-17F+ cells. Receiver operating characteristic curve analysis evidenced predictive cutoff values of bronchial neutrophils and nasal/bronchial IL-17F for discriminating between asthmatics and controls, between MAs and SAs and between FEs and non-FEs. IL-17F protein increased in bronchial/nasal lysates of SAs and FEs and in bronchial tissue of fatal asthma. IL-17F colocalized in CD4+/CD8+ cells.

Conclusions: IL-17-related cytokines expression was amplified in bronchial/nasal mucosa of neutrophilic asthma prone to exacerbation, suggesting a pathogenic role of IL-17F in FEs.

Keywords: IL-17F; Severe asthma; bronchial biopsy; endotype; frequent exacerbators; nasal biopsy; neutrophils; phenotype.

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