Hans Jürgen Hoffmann

Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK

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BACKGROUND: Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity.

METHODS: We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with 2-2.5-fold increasing allergen doses in 10 steps starting at 1/1,000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 minutes of allergen stimulation (n=7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n=10).

RESULTS: Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, p<0.0001). CD63 MFI expression was reduced from 68,248 (29,336-92,001) to 30,496 (14,046-46,179, p<0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen, resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, p=0.16 compared to grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, p=0.047) and correlated with decrease in CD63 upregulation (n=7, r>0.79, p<0.05).

CONCLUSION: Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalAllergy: European Journal of Allergy and Clinical Immunology
ISSN0105-4538
DOIs
Publication statusPublished - 10 Jul 2014

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