Imperial College London
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ProfessorStephenDurham

Faculty of Medicine, National Heart & Lung Institute

Professor of Allergy and Respiratory
 
 
 
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Contact

 

+44 (0)20 7351 8024s.durham

 
 
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Location

 

Fulham RoadRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Shamji:2019:10.1016/j.jaci.2018.09.039,
author = {Shamji, MH and Kappen, J and Abubakar-Waziri, H and Zhang, J and Steveling, E and Watchman, S and Kouser, L and Eifan, A and Switzer, A and Varrichi, G and Marone, G and Couto-Francisco, NC and Calderon, M and Durham, SR},
doi = {10.1016/j.jaci.2018.09.039},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1067--1076},
title = {Nasal allergen neutralising IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy},
url = {http://dx.doi.org/10.1016/j.jaci.2018.09.039},
volume = {143},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Shamji,MH
AU  - Kappen,J
AU  - Abubakar-Waziri,H
AU  - Zhang,J
AU  - Steveling,E
AU  - Watchman,S
AU  - Kouser,L
AU  - Eifan,A
AU  - Switzer,A
AU  - Varrichi,G
AU  - Marone,G
AU  - Couto-Francisco,NC
AU  - Calderon,M
AU  - Durham,SR
DO  - 10.1016/j.jaci.2018.09.039
EP  - 1076
PY  - 2019///
SN  - 0091-6749
SP  - 1067
TI  - Nasal allergen neutralising IgG4 antibodies block IgE-mediated responses: novel biomarker of subcutaneous grass pollen immunotherapy
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2018.09.039
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30445057
UR  - http://hdl.handle.net/10044/1/65397
VL  - 143
ER  -
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