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

Laura Hesse, Nienke van Ieperen, Corine Habraken, Arjen H Petersen, Silvia Korn, Tim Smilda, Betty Goedewaagen, Marcel H Ruiters, Adrianus C van der Graaf, Martijn C Nawijn

OnderzoeksoutputAcademicpeer review

25 Citaten (Scopus)
2161 Downloads (Pure)

Samenvatting

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.

Originele taal-2English
Pagina's (van-tot)862-874
Aantal pagina's13
TijdschriftAllergy
Volume73
Nummer van het tijdschrift4
Vroegere onlinedatum10-jan-2018
DOI's
StatusPublished - apr-2018

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