Cited by 237Allergic Rhinitis and SensitizationFood Allergy and Anaphylaxis ResearchAsthma and respiratory diseases

Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement

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Orengo, J. M., Radin, A. R., Kamat, V., Badithe, A., Ben, L. H., Bennett, B. L., Zhong, S., Birchard, D. +15 more·2018·Nature Communications

Abstract

Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.

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  1. [8]Circassia. Circassia announces top-line results from cat allergy phase III study. http://www.circassia.com/media/press-releases/circassia-announces-top-line-results-from-cat-allergy-phase-III-study. Accessed: 30 June 2016 (2016).
  2. [36]Circassia. Circassia aunnounces top-line results from house dust mite allergy field study. http://www.circassia.com/media/press-releases/circassia-announces-top-line-results-from-house-dust-mite-allergy-field-study/ Accessed: 19 April 2017 (2017).

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Authors
Orengo, J. M., Radin, A. R., Kamat, V., Badithe, A., Ben, L. H., Bennett, B. L., Zhong, S., Birchard, D., Limnander, A., Rafique, A., Bautista, J., Kostic, A., Newell, D., Duan, X., Franklin, M. C., Olson, W., Huang, T., Gandhi, N. A., Lipsich, L., Stahl, N., Papadopoulos, N. J., Murphy, A. J., & Yancopoulos, G. D.
Affiliations
Regeneron (United States) (US)
Corresponding author
Orengo, J. M.
Venue
Nature Communications
Published
2018-04-12
Volume
9
Issue
1
Pages
1421-1421
ISSN
2041-1723 (ISSN-L)
OpenAlex
W2797705783
Cited by
237
References
68
Citations by year
2026: 17 · 2025: 22 · 2024: 32 · 2023: 36 · 2022: 24 · 2021: 35 · 2020: 37 · 2019: 24 · 2018: 10
FWCI
23.52
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • OSTI OAI (U.S. Department of Energy Office of Scientific and Technical Information) (submittedVersion)
Funders
  • Howard Hughes Medical Institute (DE-AC02-05CH11231)
  • U.S. Department of Energy (-AC02-05CH11231, Contract No. DE-AC02-05-CH11231, 05CH11231, No. DE-AC02-05-CH11231, DE AC02 05CH11231, DE-AC02-)
  • Regeneron Pharmaceuticals
  • National Institutes of Health (DE-AC02–05CH11231)
  • Office of Science (No. DE-AC02- 05-CH11231, DEAC02–05CH11231, AC02-05CH11231, DE-AC02, Contract No. DE-AC02-05CH11231)
  • National Institute of General Medical Sciences (DE-AC02-05CH11231)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Allergic Rhinitis and Sensitization
  • Health Sciences › Medicine › Immunology and Allergy › Food Allergy and Anaphylaxis Research
  • Health Sciences › Medicine › Physiology › Asthma and respiratory diseases
Keywords
cat allergy, Fel d 1, allergen-specific IgG, monoclonal antibodies, allergen immunotherapy, allergen sensitization, nasal provocation, allergic airway inflammation
MeSH terms
Animal Fur, Adolescent, Adult, Allergens, Animals, Antibodies, Monoclonal, Binding, Competitive, Cats, Desensitization, Immunologic, Disease Models, Animal, Female, Glycoproteins, Humans, Hypersensitivity, Immunoglobulin E, Immunoglobulin G, Male, Middle Aged, Protein Binding, Receptors, IgE, Complex Mixtures, Mice

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