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

Hesse, L., van Ieperen, N., Habraken, C., Petersen, A. H., Korn, S., Smilda, T., Goedewaagen, B., Ruiters, M. H., van der Graaf, A. C. & Nawijn, M. C., Apr-2018, In : Allergy. 73, 4, p. 862-874 13 p.

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BackgroundAllergen-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 -glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment.

AimsHere, 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 methodsHDM-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.

ResultsESR 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.

DiscussionTaken 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.

ConclusionsWe postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.

Original languageEnglish
Pages (from-to)862-874
Number of pages13
JournalAllergy
Volume73
Issue number4
Early online date10-Jan-2018
Publication statusPublished - Apr-2018

    Keywords

  • Allergen-specific immunotherapy, allergic asthma, house dust mites, purified natural Der p1 and 2, tolerance induction, HOUSE-DUST MITE, ALLERGEN-SPECIFIC IMMUNOTHERAPY, DERMATOPHAGOIDES-PTERONYSSINUS, AIRWAY INFLAMMATION, RESPONSES, VACCINES, DER-P-1, FARINAE, GENES, CELLS

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