Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model |
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| Authors: | L Hesse N van Ieperen C Habraken A H Petersen S Korn T Smilda B Goedewaagen M H Ruiters A C van der Graaf M C Nawijn |
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| Institution: | 1. Experimental Pulmonary and Inflammatory Research (EXPIRE), Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;2. Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;3. Department of Pathology & Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;4. Citeq Biologics BV, Groningen, The Netherlands |
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| Abstract: | 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. |
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| Keywords: | Allergen‐specific immunotherapy allergic asthma house dust mites purified natural Der p1 and 2 tolerance induction |
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