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Intact allergens: Faster internalization in dendritic cells and stronger in-vitro activation of T cells

The results of a recent study by Heydenreich et al. demonstrate that intact allergens induce both significantly increased proliferation and increased cytokine production of CD4+ T cells in vitro compared to glutaraldehyde-modified allergoids (1). Both are used as markers for the immunogenicity of a specific immunotherapy. The content of functionally intact allergens is therefore an important argument for subcutaneous immunotherapy (SCIT) with AVANZ®. Another study has already shown that this preparation has a significant immunological effect and is very well tolerated (2).

Heydenreich et al. in their study analyzed the differences between intact allergens and allergoids in terms of both internalization and T cell and basophil activation. For this purpose, human monocyte-derived dendritic cells (DCs) were incubated with intact allergens from grass or birch pollen or with corresponding glutaraldehyde-modified allergoids.

In this study, the authors demonstrated that functionally intact allergens induce higher T cell proliferation in vitro compared to glutaraldehyde-modified allergoids. The T cell proliferation serves as an indication of the immunogenicity of the preparations. The background to the significantly lower T cell proliferation of glutaraldehyde-modified allergoids is the significantly slower uptake of glutaraldehyde allergoids into dendritic cells. A further comparison shows that dendritic cells incubated with functionally intact allergens induce a higher interleukin release in CD4+ T cells in vitro than DCs incubated with glutaraldehyde allergoids. The majority of allergoids currently on the market are denatured with glutaraldehyde.

The study once again proves that the allergoid concept described by Marsh in 1970 (3), by denaturing intact allergens with aldehydes, reducing allergenicity without affecting immunogenicity cannot be maintained. Instead, a reduction in allergenicity is also accompanied by a reduction in immunogenicity.

(1) Heydenreich B et al., Immunology 2012; 136(2):208-17
(2) Pfaar O et al, Allergy 2012; 67:630-637
(3) Marsh D et al., Immunology 1970; 18:705-22

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