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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.
Afiliación
  • Hesse L; Experimental Pulmonary and Inflammatory Research (EXPIRE), Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • van Ieperen N; Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Habraken C; Experimental Pulmonary and Inflammatory Research (EXPIRE), Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Petersen AH; Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Korn S; Experimental Pulmonary and Inflammatory Research (EXPIRE), Department of Pathology & Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Smilda T; Groningen Research Institute of Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Goedewaagen B; Department of Pathology & Medical Biology, Medical Biology Section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
  • Ruiters MH; Citeq Biologics BV, Groningen, The Netherlands.
  • van der Graaf AC; Citeq Biologics BV, Groningen, The Netherlands.
  • Nawijn MC; Citeq Biologics BV, Groningen, The Netherlands.
Allergy ; 73(4): 862-874, 2018 04.
Article en En | MEDLINE | ID: mdl-29318623
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 ß-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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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Cisteína Endopeptidasas / Desensibilización Inmunológica / Antígenos Dermatofagoides / Proteínas de Artrópodos Límite: Animals Idioma: En Revista: Allergy Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Dinamarca
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Asma / Cisteína Endopeptidasas / Desensibilización Inmunológica / Antígenos Dermatofagoides / Proteínas de Artrópodos Límite: Animals Idioma: En Revista: Allergy Año: 2018 Tipo del documento: Article País de afiliación: Países Bajos Pais de publicación: Dinamarca