Early effect of ultrarush venom immunotherapy on the IgG antibody response

Background: We have previously shown in several allergy models that allergic and tolerance status with respect to allergens is associated with a somewhat different dominant specificity of IgG antibodies. The objective was to test this hypothesis in the compelling model of ultrarush venom immunotherapy (VIT), which induces clinical tolerance after only a few hours of treatment. 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 days). 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 binding of pooled IgG from allergic patients changed rapidly, with mean percentage 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, respectively (P < 0.001 by one-way ANOVA). The capacity of individual sera to prevent the antigen binding of pooled IgG from patients receiving prolonged VIT 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 specificity, i.e., a change in the set of epitopes dominantly recognized by IgG on wasp-venom antigens, occurred concomitantly with early clinical tolerance and was already detectable a few hours after the onset of treatment. Although it may be an epiphenomenon, this change represents the earliest humoral modification described so far during this procedure. The mechanism is unknown, but it appears to be a selective depletion of the highest avidity antibody fraction by the venom injected in large doses at this stage of therapy. Finally, our data now show the previously documented association between a particular IgG specificity and the clinical status (allergy vs tolerance) to be true also with ultrarush VIT, a model in which the clinical ability to display allergic symptoms is rapidly reversed.