Klunker, S. et al. Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding. J. Allergy Clin. Immunol. 120, 688-695

Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, United Kingdom.
Journal of Allergy and Clinical Immunology (Impact Factor: 11.48). 10/2007; 120(3):688-95. DOI: 10.1016/j.jaci.2007.05.034
Source: PubMed


The combination of anti-IgE (omalizumab) therapy with ragweed injection immunotherapy for seasonal allergic rhinitis results in a significant reduction in systemic side effects and enhanced efficacy compared with immunotherapy alone. One proposed mechanism of immunotherapy is to induce regulatory antibodies that inhibit facilitated antigen presentation.
We sought to determine whether the combination protocol has a cumulative effect on inhibition of facilitated antigen presentation both during and after discontinuation of treatment.
Ragweed allergen immunotherapy with and without omalizumab therapy was tested in a 4-arm, double-blind, placebo-controlled study. Flow cytometry was used to detect serum inhibitory activity for IgE-facilitated CD23-dependent allergen binding to B cells as a surrogate marker for facilitated antigen presentation. Serum ragweed-specific IgG4 was measured by means of ELISA.
Immunotherapy alone resulted in partial inhibition of allergen-IgE binding after 5 to 19 weeks of treatment compared with baseline (P < .01). Complete inhibition of allergen-specific IgE binding was observed in both treatment groups receiving omalizumab (P < .001). Allergen-specific IgG4 levels were only increased after immunotherapy (P < .05), both in the presence and absence of anti-IgE treatment. Combined treatment resulted in the induction of long-lasting inhibitory antibody function for up to 42 weeks compared with either treatment alone.
Ragweed immunotherapy induced serum regulatory antibodies that partially blocked binding of allergen-IgE complexes to B cells. Additional treatment with anti-IgE, by directly blocking IgE binding to CD23, completely inhibited allergen-IgE binding.
The combination of ragweed immunotherapy and anti-IgE resulted in prolonged inhibition of allergen-IgE binding compared with either treatment alone, events that might contribute to enhanced efficacy.

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    • "In addition to physical fusion, there is also a huge potential for combining o conventional and novel methods of AIT with immune response modifiers. For example, anti-IgE combined with AIT has been evaluated in several studies [24], and resulted in a significant decrease in the risk of anaphylaxis caused by rush immunotherapy (a rapid dose increment approach to reach the maintenance dose as quick as possible) and improved rescue medication scores (the need for a rescue medication to suppress the symptoms: for example anti-histamines for allergic rhinitis) of AIT with a good safety profile [24,44]. In a recent study, eighteen weeks' treatment of omalizumab in combination with AIT in patients with seasonal allergic rhinitis and comorbid seasonal allergic asthma reduced the symptom load during the treatment period but showed no prolonged effect during treatment with AIT only [25]. "
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    ABSTRACT: Allergen-specific immunotherapy (SIT) represents the only curative and specific way for the treatment of allergic diseases, which have reached a pandemic dimension in industrial countries affecting up to 20-30% of the population. Although applied for 100 years to cure allergy, SIT still faces several problems related to side effects and limited efficacy. Currently, allergen-SIT is performed with vaccines based on allergen extracts that can cause severe, often life threatening, anaphylactic reactions as well as new IgE sensitization to other allergens present in the extract. Low patient adherence and high costs due to long duration (3 to 5 years) of treatment have been commonly reported. Several strategies have been developed to tackle these issues and it became possible to produce recombinant allergen-SIT vaccines with reduced allergenic activity.
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    • "In addition to its effects on immediate hypersensitivity, omalizumab also downregulates FcεRI expression by dendritic cells[9,10]. Serum from omalizumab treated patients effectively blocks CD23 mediated facilitated allergen binding to B cells[11]. Because of these multifunctional activities of FcεRI and CD23 beyond immediate hypersensitivity and the ability of omalizumab to block IgE binding to both of these receptors, it has been postulated that anti-IgE therapy may have in vivo immunomodulatory activity on T cell responses[8]. "
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