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- Neimert-Andersson, T., et al.
(author)
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Carbohydrate-based particles reduce allergic inflammation in a mouse model for cat allergy
- 2008
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 63:5, s. 518-526
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Journal article (peer-reviewed)abstract
- Background: Allergen-specific immunotherapy (ASIT) is the only treatment of allergic disease that gives long-lasting relief of symptoms. However, concerns for safety and efficiency have highlighted the need for improvement of the therapy. We have previously suggested carbohydrate-based particles (CBPs) as a novel adjuvant and allergen carrier for ASIT. Our aim of this study was to evaluate the therapeutic potential of CBPs in ASIT, employing a mouse model for cat allergy. Methods: BALB/c mice were subcutaneously immunized with the recombinant (r) cat allergen Fel d 1 followed by intranasal challenge with cat dander extract (CDE). The sensitized mice were therapeutically treated with rFel d 1 covalently coupled to CBPs (CBP-rFel d 1). Airway hyper-reactivity (AHR), infiltration of leucocytes in bronchoalveolar lavage (BAL) fluid, allergen-specific serum immunoglobulin levels and in vitro splenocyte responses were evaluated. Results: Mice treated with CBP-rFel d 1 showed reduced features of allergic inflammation. They responded with (i) significantly decreased AHR and infiltration of eosinophils in BAL fluid after CDE challenge, (ii) the serum level of rFel d 1-specific IgE was reduced and the level of IgG(2)a was more pronounced after CBP-rFel d 1 treatment, and (iii) there was also a tendency of decreased allergen-specific cellular response. Conclusions: Carbohydrate-based particles are effective tools as adjuvant and allergen carriers for use in ASIT and constitutes a promising strategy to improve allergy treatment.
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- Vilhelmsson, M, et al.
(author)
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The Malassezia sympodialis allergen Mala s 11 induces human dendritic cell maturation, in contrast to its human homologue manganese superoxide dismutase
- 2007
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In: International archives of allergy and immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 143:2, s. 155-162
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Journal article (peer-reviewed)abstract
- <i>Background:</i> Recently, we identified a major <i>Malassezia sympodialis</i> allergen, Mala s 11, which displays a high degree of DNA sequence homology to human manganese superoxide dismutase (hMnSOD). In atopic eczema patients sensitized to <i>M. sympodialis</i>, hMnSOD can elicit eczematous reactions and positive skin prick tests, suggesting cross- reactivity to Mala s 11 based on molecular mimicry. The objective of the current study was to compare the influence of Mala s 11 and hMnSOD on human dendritic antigen-presenting cells. <i>Methods:</i> Monocyte-derived dendritic cells (MDDCs) from healthy blood donors were co-cultured with recombinant Mala s 11 (rMala s 11), recombinant hMnSOD (rhMnSOD), lipopolysaccharide or cultured in medium alone. Phenotypic changes were analysed using flow cytometry and allogeneic lymphocyte proliferation assays. Cytokine release into culture supernatants was investigated using cytometric bead array. <i>Results:</i> Whereas rhMnSOD did not affect the MDDC phenotype, rMala s 11 up-regulated the maturation marker CD83, the co-stimulatory molecules CD40, CD80, CD86 and HLA-DR to a similar extent as lipopolysaccharide. Furthermore, rMala s 11, but not rhMnSOD, induced significantly higher levels of TNF-α, IL-6, IL-8, IL-10 and IL-12p70 in the culture supernatants at 24 h in comparison with MDDCs cultured in medium alone. Finally, MDDCs pre-incubated with rMala s 11 induced a significantly higher proliferation of allogeneic CD14-depleted peripheral blood monocytes than MDDCs pre-incubated with rhMnSOD. <i>Conclusion:</i> Our results suggest that Mala s 11, but not hMnSOD, affects the immune response of healthy individuals through dendritic cell maturation and cytokine release. This indicates that dendritic cells possess the ability to distinguish between Mala s 11 and its human homologue MnSOD.
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