Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model

Background Allergen‐specific immunotherapy can induce long‐term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β‐glucans, chi...

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Bibliographic Details
Published in:Allergy (Copenhagen) 2018-04, Vol.73 (4), p.862-874
Main Authors: Hesse, L., Ieperen, N., Habraken, C., Petersen, A. H., Korn, S., Smilda, T., Goedewaagen, B., Ruiters, M. H., Graaf, A. C., Nawijn, M. C.
Format: Article
Language:English
Subjects:
Allergens
Allergen‐specific immunotherapy
allergic asthma
Allergic rhinitis
Allergies
Alveoli
Animals
Antigens, Dermatophagoides - administration & dosage
Antigens, Dermatophagoides - immunology
Arthropod Proteins - administration & dosage
Arthropod Proteins - immunology
Asthma
Asthma - immunology
Bronchus
CCL17 protein
CCL20 protein
Cysteine Endopeptidases - administration & dosage
Cysteine Endopeptidases - immunology
Cytokines
Data processing
Dermatophagoides pteronyssinus
Desensitization, Immunologic - methods
Disease Models, Animal
Eotaxin
Epithelium
Glucans
Helper cells
House dust
house dust mites
Hypersensitivity
Immunity
Immunostimulation
Immunotherapy
Inflammation
Injections, Subcutaneous
Leukocytes (eosinophilic)
Lungs
Lymphocytes T
Mice
Original
ORIGINAL ARTICLES
purified natural Der p1 and 2
Respiratory tract
Rhinitis
tolerance induction
β-Glucan
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Summary:Background Allergen‐specific immunotherapy can induce long‐term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β‐glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment. Aims Here, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM)‐driven mouse model of allergic asthma. Materials and methods HDM‐sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen‐induced ear swelling response (ESR), airway hyperresponsiveness (AHR), and inflammation in bronchoalveolar lavage fluid (BAL) and lung tissue. Results ESR measurement shows suppression of early allergic response in HDM‐SCIT– and DerP1/2‐SCIT–treated mice. Both HDM‐SCIT and DerP1/2‐SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2‐SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2‐SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL‐33, CCL17 and eotaxin levels in lung tissue. Discussion Taken together, these data show that purified DerP1/2‐SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM‐induced activation of lung structural cells including airway epithelium. Conclusions We postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.
ISSN:0105-4538
1398-9995
DOI:10.1111/all.13382