Early effect of ultrarush venom immunotherapy on the IgG antibody response

Background: We have previously shown in several allergy models that allergi c and tolerance status with respect to allergens is associated with a somew hat different dominant specificity of IgG antibodies. The objective was to test this hypothesis in the compelling model of ultrarush venom immunothera py (VIT), which induces clinical tolerance after only a few hours of treatm ent. Methods: Antibody titers and specificity were evaluated through solid-phase ELISA using streptavidin-biotin technology in 12 patients allergic to wasp venom before and during the ultrarush procedure (at 12 h, 24 h, and 15 day s). The results were compared with those from another group of 20 patients treated with venom injections for at least 2 years. Results: No significant change was observed in IgG titers during the early phase of VIT. The capacity of individual sera to prevent the antigen bindin g of pooled IgG from allergic patients changed rapidly, with mean percentag e inhibitions falling from 80 +/- 15%, before starting VIT, to 26 +/- 14%, 35 +/- 15%, and 34 +/- 5% after 12 h, 24 h, and 15 days of treatment, respe ctively (P < 0.001 by one-way ANOVA). The capacity of individual sera to pr event the antigen binding of pooled IgG from patients receiving prolonged V IT changed, with mean percent inhibitions increasing from 47 +/- 8%, before starting VIT, to 76 +/- 7%, 83 +/- 6%, and 87 +/- 6% after 12 h, 24 h, and 15 days of treatment, respectively (P < 0.001 by one-way ANOVA). Conclusions: During the initial phase of ultrarush VIT, a change in IgG spe cificity, i.e., a change in the set of epitopes dominantly recognized by Ig G on wasp-venom antigens, occurred concomitantly with early clinical tolera nce and was already detectable a few hours after the onset of treatment. Al though it may be an epiphenomenon, this change represents the earliest humo ral modification described so far during this procedure. The mechanism is u nknown, but it appears to be a selective depletion of the highest avidity a ntibody fraction by the venom injected in large doses at this stage of ther apy. Finally, our data now show the previously documented association betwe en a particular IgG specificity and the clinical status (allergy vs toleran ce) to be true also with ultrarush VIT, a model in which the clinical abili ty to display allergic symptoms is rapidly reversed.