Klunker-Anti-IgE Therapy Inhibits IgE-facilitated Allergen Presentation and Increases the Efficacy of Ragweed Immunotherapy

Rationale: The combination of anti-IgE (omalizumab) with rush ragweed injection immunotherapy (IT) for seasonal allergic rhinitis resulted in an 80 percent reduction in systemic side effects and enhanced efficacy versus immunotherapy alone (Casale T. B. et al., 2005). We tested IgG4 antibody levels and serum inhibitory activity for allergen-IgE binding to B cells in a ’functional’ assay of IgG before/during treatment.

Methods: The combination of ragweed IT and omalizumab therapy was tested in a four-arm, double-blind, placebo-controlled study. Serum ragweed-specific IgG4 was measured by ELISA. Flow cytometry was used to detect serum inhibitory activity for IgE-facilitated CD23-dependent allergen binding to B-cells, a surrogate marker for facilitated allergen presentation.

Results: Seasonal daily rhinitis symptom scores after IT + omalizumab (mean+/-SE, 0.56+/-0.146)  were lower compared to IT + placebo (0.91+/-0.151) (p=0.05). Allergen-specific IgG4 levels were increased after IT from as early as week 5 (1 week after rush IT) (p<0.05) until week 19 (anti-IgE + IT 2.05 fold+/-0.23, placebo + IT 3.34 fold +/- 1.50) (p<0.05,) but not after omalizumab alone (1.05 fold+/-0.18). IT resulted in partial inhibition of allergen-IgE binding after 5 -19 weeks compared to baseline (p<0.01). Complete inhibition of allergen-specific IgE binding was observed in the treatment groups receiving omalizumab (p<0.001).

Conclusion: Ragweed IT induced elevated serum IgG4 antibodies which partially blocked allergen-IgE binding to B cells, whereas treatment with anti-IgE, by removing free serum IgE, completely inhibited facilitated antigen presentation, events which may have contributed to enhanced efficacy with the combination of anti-IgE therapy and IT.

Journal of Allergy and Clinical Immunology Vol. 117 (2) S89: 2006.