Presented at:
XXVI Congress of the European Academy of Allergology and Clinical Immunology
Goteborg, Sweden, June 9-13, 2007
The combination of anti-IgE monoclonal antibody (omalizumab) with ragweed immunotherapy results in enhanced and long-term inhibitory effects on facilitated-antigen presentation
Francis JN, Saggar LR, Seyfert-Margolis V, Asare AL, Klunker S, Casale TB, Durham SR and Immune Tolerance Network Group.
Background: The combination of anti-IgE therapy (omalizumab) with a rush protocol of ragweed injection immunotherapy (IT) for seasonal allergic rhinitis results in a significant reduction in systemic side effects and an enhanced efficacy for the combination compared to immunotherapy alone. One proposed mechanism of immunotherapy is to induce regulatory antibodies that inhibit facilitated antigen presentation (FAP). Our previous studies have shown that serum obtained after ragweed immunotherapy partially inhibited the binding of allergen-IgE complexes to B cells (FAB) whereas anti-IgE treatment completely inhibited serum FAB activity. The purpose of this study was to determine the long-term effects of treatment on FAP after treatment withdrawal.
Methods: In patients with seasonal ragweed asthma, ragweed allergen immunotherapy which employed a rush protocol with and without omalizumab therapy was tested in a four-arm, double-blind, parallel group, placebo-controlled study. Serum samples were tested at baseline, at the end of treatment and at intervals up 42 weeks thereafter. Flow cytometry was used to detect serum inhibitory activity for IgE-facilitated CD23-dependent allergen binding to B-cells as a surrogate marker for FAP. Serum ragweed-specific IgG4 was measured by ELISA.
Results: Immunotherapy alone resulted in partial inhibition of allergen-IgE binding at the end of treatment compared to baseline (P<0.01). However, inhibitory activity was no longer detectable in samples 18 weeks after withdrawal of immunotherapy. Complete inhibition of allergen-specific IgE binding was observed in treatment groups receiving omalizumab at the end of treatment (P<0.001). Serum obtained from subjects treated with anti-IgE alone showed significant inhibitory properties up to 30 weeks after drug withdrawal. In contrast, serum from subjects treated with both immunotherapy and anti-IgE could significantly inhibit binding for at least 42 weeks after treatment cessation (binding at 42 weeks; anti-IgE + IT=40±9%, P<0.01; IT alone=77±14%, anti-IgE alone=84±7%; placebo=100±9%). Allergen-specific IgG4 levels were increased after immunotherapy (P<0.05), both in the presence and absence of anti-IgE treatment, and did not persist after treatment withdrawal.
Conclusion: The combination of anti-IgE treatment with ragweed immunotherapy resulted in the induction of long lasting inhibitory activity for FAB that persisted for at least one year when compared to pre-treatment levels.