Nasal allergen neutralising IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy
File(s)
Author(s)
Type
Journal Article
Abstract
BACKGROUND: Grass pollen subcutaneous immunotherapy (SCIT) is associated with induction of serum IgG4-associated inhibitory antibodies that prevent IgE-facilitated allergen binding to B cells. OBJECTIVE: To determine whether SCIT induces nasal allergen-specific IgG4 antibodies with inhibitory activity that correlate closely with clinical response. METHODS: In a cross-sectional, controlled study, nasal fluid and sera were collected during the grass pollen season from 10 SCIT-treated patients, 13 untreated allergics (SAR) and 12 non-atopic controls (NA). Nasal and serum IgE and IgG4 to Phleum pratense (Phl p) components were measured by ISAC microarray. Inhibitory activity was measured by IgE-FAB assay. IL-10+Breg cells were quantified in peripheral blood by flow cytometry. RESULTS: Nasal and serum Phl p1 and Phl p5-specific IgE levels were elevated in SAR compared to NA (all, P < .001) and SCIT group. Nasal IgG4 levels were increased in SCIT compared to SAR group (P < .001) during the pollen season compared to out of season. IgG-associated inhibitory activity in nasal fluid and serum was significantly increased in SCIT compared to SAR group (both, P < .001). The magnitude of the inhibitory activity was 96% in the nasal fluid compared to 66% in serum and was reversed following depletion of IgG in nasal fluid (P = .03) and serum (P = .002). Both nasal fluid (r = -0.67, P = .0011) and serum (r = -0.59, P = .0097) blocking activity correlated global symptom improvement. IL-10+Breg cells were increased in season compared to out of season in SCIT group (P < .01). CONCLUSION: For the first time, we show that nasal IgG4-associated inhibitory activity correlate closely with the clinical response to allergen immunotherapy in allergic rhinitis with/without asthma.
Date Issued
2019-03-01
Date Acceptance
2018-09-28
Citation
Journal of Allergy and Clinical Immunology, 2019, 143 (3), pp.1067-1076
ISSN
0091-6749
Publisher
Elsevier
Start Page
1067
End Page
1076
Journal / Book Title
Journal of Allergy and Clinical Immunology
Volume
143
Issue
3
Copyright Statement
© 2018 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology. This manuscript is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licence http://creativecommons.org/licenses/by-nc-nd/4.0/
Sponsor
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/30445057
PII: S0091-6749(18)31595-1
Grant Number
G0601303
G1000758
G1000758
Subjects
Biomarkers of allergen immunotherapy
IgA(1)
IgA(2)
IgE-FAB
IgG(4)
Subcutaneous immunotherapy
allergic rhinoconjunctivitis with and without asthma
blocking antibodies
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-11-14