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Background An important advantage of allergen immunotherapy as compared to pharmacotherapy for allergic rhinitis is the long-term effect that persists after completing immunotherapy. The mechanism of the sustained effect of allergen immunotherapy is not completely understood. Methods We conducted a 7-year study of monitoring allergen-specific basophil response and serological markers in 20 subjects with moderate-to-severe grass pollen-allergic rhinitis just before beginning and after up-dosing of subcutaneous grass pollen immunotherapy, before the first pollen season, and 1–2 years after completion of 3–5 years of treatment. Comparable untreated rhinitis subjects were followed at the same time points. Clinical outcomes included assessment of symptoms, use of rescue medication, and quality of life. The basophil response was also monitored after removal of IgG antibodies. Results Basophil response assessed as area under the curve (AUC) halved during initiation of SCIT and was 55% lower 1–2 years after completing SCIT. In the untreated group, the basophil response remained comparable. Although immunotherapy-induced grass pollen-specific IgG4 levels decreased to near pre-immunotherapy levels after completing SCIT, the removal of IgG antibodies resulted in an increase in basophil response almost to the pre-immunotherapy levels. In untreated subjects, removal of IgG did not have any effect on basophil response. Conclusions Grass pollen immunotherapy induces sustained suppression of the allergen-specific basophil response that persists after completion of treatment and could account for long-term clinical tolerance. It also seems to be associated with persistent blocking activity of IgG antibodies.

Background: Systemic side-effects of venom immunotherapy (VIT) represent a considerable problem in the treatment of patients allergic to Hymenoptera venom. We examined the hypothesis whether basophil responsiveness might be connected with the adverse reactions to VIT. Methods: Basophil surface expression of activation marker CD63 induced by different concentrations of honeybee and wasp venom (0.1 and 1 μg/ml) was measured by flow cytometry in 34 patients with history of systemic anaphylactic reactions to Hymenoptera sting just before rush honeybee or wasp VIT. Results: Eleven of 34 patients had systemic anaphylactic reaction (Mueller grades I–III) and one patient a large local reaction to VIT. In those 12 patients, median percentage of activated basophils after stimulation with VIT-specific venom in concentration of 0.1 μg/ml was 99% (range: 17–195) of value reached with stimulation with 1 μg/ml. Side-effects occurred in all patients with 0.1/1 ratios over 92% (eight of 12). In contrast, in 22 patients with no side-effects, the median 0.1/1 ratio was 25% (range: 2–92). These concentration-dependent activation ratios were significantly different between the groups with and without side reactions (P

Background The precise immunological mechanisms for the early clinical protection of venom immunotherapy (VIT) have not yet been explained. Our aim was to evaluate whether high-affinity IgE receptor (FceRI) and the related basophil function have a role in the induction of short-term VIT protection. Methods We included 60 adults and 48 children. Basophil threshold sensitivity (CD-sens) to anti-FceRI stimulation, and FceRI gene and cell-surface expression were assessed at the beginning and just before the first maintenance dose (MD) of 100 μg of ultra-rush VIT (day 5) and at the beginning, during buildup, and just before the first MD of 70 μg and of 100 μg of semi-rush VIT (weeks 1–2 and 5). Results We demonstrated a significant reduction in CD-sens to anti-FceRI stimulation before the first MD in both ultra-rush and semi-rush VIT in all included subjects. FceRI gene and/or cell-surface expression was decreased in 34–100% of subjects, with different dynamics between VIT protocols. Conclusion We found a marked desensitization of FceRI-activated basophils after short-term VIT. This suppression, which could be highly relevant for the development of early protective mechanisms, might be also related to the changes at the level of FceRI expression.

Background There is no in vitro test to predict the induction of long-term tolerance in patients treated with venom immunotherapy (VIT). The aim of this study was to investigate whether immunotherapy-induced changes in basophil responsiveness reflect a state of protection and the induction of a tolerance. Methods Twenty-three patients with allergic reaction after Hymenoptera sting (11 wasp and 12 honeybee) were treated with VIT. In all patients, a CD63 basophil activation test was performed before the beginning of immunotherapy, after 1 year and after completing 4–6.5 years of immunotherapy (approximately 1 year after stopping). The tolerance was then evaluated by a sting challenge test. The basophil activation test was repeated 3–6 months after the challenge. Results Twenty-two subjects showed a negative sting challenge, and one subject, a positive sting challenge. Allergen-specific basophil response remained unchanged after 1 year of immunotherapy. However, after immunotherapy, a significant and approximately fourfold decrease was demonstrated in all tolerant subjects mainly in response to submaximal 0.1 μg/ml allergen concentration. This depression was sustained and did not change with the sting challenge test. In a nontolerant patient with a positive sting challenge, basophil response did not change. Conclusions Our results suggest that the depression of allergen-specific basophil response seems to be associated with the induction of a tolerance after completing a course of VIT.