Local and systemic effects of cat allergen nasal provocation
File(s)
Author(s)
Type
Journal Article
Abstract
Background
Cat allergen is widely distributed in homes and schools; allergic sensitization is common.
Objective
To develop a model of cat allergen nasal challenge to establish dose–response and time–course characteristics and investigate local and systemic biomarkers of allergic inflammation.
Methods
Nineteen cat‐allergic individuals underwent titrated nasal challenge, range 0.243 to 14.6 μg/mL Fel d1, and matched diluent‐only provocation. Clinical response to 8 h was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Nasal fluid was collected using polyurethane sponges and analysed by ImmunoCAP and multiplex assays. Whole blood flow cytometry for basophil surface CD63, CD107a, and CD203c was carried out at baseline and 6 h post‐challenge.
Results
A dose–response to allergen was seen in symptom scores and PNIF, maximal at 10 000 BU/mL (4.87 μg/mL Fel d1), P < 0.0001 vs. diluent. Nasal fluid tryptase was elevated at 5 min after challenge (P < 0.05 vs. diluent); eotaxin, IL‐4, ‐5, ‐9, and ‐13 were increased at 8 h (P < 0.05 to P < 0.0001 vs. diluent); TSLP was undetectable; IL‐10, IL‐17A, and IL‐33 were unchanged compared to diluent challenge. Nasal fluid IL‐5 and IL‐13 correlated inversely with PNIF after challenge (IL‐5, r = −0.79, P < 0.0001; IL‐13, r = −0.60, P = 0.006). Surface expression of CD63 and CD107a was greater at 6 h than at baseline, both in the presence (both P < 0.05) and absence (CD63, P < 0.01; CD107a, P < 0.05) of in vitro allergen stimulation; no changes were seen on diluent challenge day.
Conclusions
Cat allergen nasal challenge produces local and systemic Th2‐driven inflammatory responses and has potential as a surrogate outcome measure in clinical trials.
Cat allergen is widely distributed in homes and schools; allergic sensitization is common.
Objective
To develop a model of cat allergen nasal challenge to establish dose–response and time–course characteristics and investigate local and systemic biomarkers of allergic inflammation.
Methods
Nineteen cat‐allergic individuals underwent titrated nasal challenge, range 0.243 to 14.6 μg/mL Fel d1, and matched diluent‐only provocation. Clinical response to 8 h was assessed by symptom scores and peak nasal inspiratory flow (PNIF). Nasal fluid was collected using polyurethane sponges and analysed by ImmunoCAP and multiplex assays. Whole blood flow cytometry for basophil surface CD63, CD107a, and CD203c was carried out at baseline and 6 h post‐challenge.
Results
A dose–response to allergen was seen in symptom scores and PNIF, maximal at 10 000 BU/mL (4.87 μg/mL Fel d1), P < 0.0001 vs. diluent. Nasal fluid tryptase was elevated at 5 min after challenge (P < 0.05 vs. diluent); eotaxin, IL‐4, ‐5, ‐9, and ‐13 were increased at 8 h (P < 0.05 to P < 0.0001 vs. diluent); TSLP was undetectable; IL‐10, IL‐17A, and IL‐33 were unchanged compared to diluent challenge. Nasal fluid IL‐5 and IL‐13 correlated inversely with PNIF after challenge (IL‐5, r = −0.79, P < 0.0001; IL‐13, r = −0.60, P = 0.006). Surface expression of CD63 and CD107a was greater at 6 h than at baseline, both in the presence (both P < 0.05) and absence (CD63, P < 0.01; CD107a, P < 0.05) of in vitro allergen stimulation; no changes were seen on diluent challenge day.
Conclusions
Cat allergen nasal challenge produces local and systemic Th2‐driven inflammatory responses and has potential as a surrogate outcome measure in clinical trials.
Date Issued
2015-03-01
Date Acceptance
2014-09-01
Citation
Clinical and Experimental Allergy, 2015, 45 (3), pp.613-623
ISSN
0954-7894
Publisher
Wiley
Start Page
613
End Page
623
Journal / Book Title
Clinical and Experimental Allergy
Volume
45
Issue
3
Copyright Statement
© 2014 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
This is an open access article under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Sponsor
Wellcome Trust
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000350455800007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Grant Number
097881/Z/11/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Allergy
Immunology
cat allergy
nasal allergen challenge
tryptase
basophil
cytokine
LOWER AIRWAYS
CHALLENGE
RHINITIS
RESPONSES
EXPOSURE
ASTHMA
INFLAMMATION
CHILDREN
RESPONSIVENESS
EOSINOPHILIA
Publication Status
Published
Date Publish Online
2014-10-09