Vespula spp. venom immunotherapy: basophil excitability and Fc_εRI/Fc_γRIIb expression

Basophils are recognized as important effector cells during the sensitization and effector phases of IgE-mediated allergy. Besides histamine release during anaphylaxis, basophils contribute to early immune polarization as an important source of Th2-associated cytokines. Vespula spp. venom immunotherapy (VIT) represents a prime example of clinically highly effective allergen-specific immunotherapy. This study investigated functional and phenotypic changes in circulating basophils during early VIT in a homogenous case series.

Twenty-four patients eligible for VIT were examined before treatment, after 3 days, and after 1 month of therapy. Basophils were primed with interleukin-(IL-)3 and stimulated with IgE-dependent triggers, including Vespula spp. venom and an anti-IgE antibody, as well as the IgE-independent bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). Basophil activation was assessed by flow cytometric measurement of CD63 expression. In parallel, Fc_εRI and Fc_γRIIb receptor expression on basophils was quantified, and serum levels of total IgE, Vespula spp. venom-specific IgE, and venom-specific IgG₄ were measured. Changes over time were tested using a mixed-effects model for repeated measures. Paired t-tests, Wilcoxon signed-rank tests, and Friedman tests were used for paired comparisons and non-parametric repeated measures.

After one month of VIT, venom-specific basophil excitability was significantly reduced. In contrast, activation by anti-IgE and fMLP remained largely unchanged. An increase of both Fc_εRI and Fc_γRIIb expression on basophils was already detectable at day 3 after starting VIT and reached statistical significance at day 28. Serologically, total IgE and Vespula spp. venom-specific IgE slightly rose during VIT, but the most pronounced increase was observed for venom-specific IgG₄.

Data of this study suggest that upregulation of Fc_γRIIb together with venom-specific IgG₄ induction drives venom-specific basophil suppression, possibly by Fc_γRIIb-Fc_εRI co-aggregation. The overall picture of venom-specific basophil activation, basophil Fc_γRIIb expression, and serum IgG₄ may serve as a biomarker of immune modulation towards tolerance.