Analysis of the Antibody Responses Induced by Subcutaneous Injection Immunotherapy with Birch and Fagales Pollen Extracts Adsorbed onto Aluminum Hydroxide

Abstract

Background: Allergen-specific subcutaneous immunotherapy (SCIT) is an antigen-specific therapy of IgE-mediated allergies. In the present study, we analyze the epitope specificities of antibody responses induced by SCIT with allergen extracts from pollen of trees belonging to the order Fagales (birch, alder, hazel) adsorbed onto aluminum hydroxide. Methods: The IgE, IgG1–4 and IgA responses to defined recombinant allergens (birch pollen: Bet v 1; alder pollen: Aln g 1; hazel pollen: Cor a 1; apple: Mal d 1) as well as to Bet v 1-derived recombinant fragments and synthetic peptides were analyzed in sera from patients who had undergone SCIT for different periods of time. Results: Long-term SCIT (>1 year; cumulative dose >1,000,000 SQ units) induced more pronounced IgG1, IgG2 and IgG4 responses to Bet v 1 and Bet v 1-related allergens according to the degree of sequence homology (Bet v 1>Aln g 1>Cor a 1>Mal d 1) than short-term SCIT (<1 year; cumulative dose <1,000,000 SQ units). In contrast to patients treated for <1 year, patients treated for >1 year mounted distinct IgG1, IgG2 and IgG4 responses against sequential Bet v 1 epitopes. No relevant allergen-specific IgA or IgG3 responses were induced by short- or long-term SCIT. Using a competitive ELISA assay, it could be shown that serum IgG from patients undergoing long-term SCIT inhibited IgE reactivity to Bet v 1 better than IgG from patients undergoing short-term SCIT. Conclusion: SCIT with allergen extracts adsorbed onto aluminum hydroxide induces IgG responses against new epitopes that block IgE binding and cross-react with structurally related allergens depending, among other factors, on duration of treatment and cumulative injected dose.

Allergenic Profile to <i>Phleum pratense</i> and Immunological Changes Induced after Grass Allergen-Specific Immunotherapy

“…There is currently a clear increase in the importance of other markers, including cytokines and other mediators [24,27]. IgG antibodies against new epitopes are induced by immunotherapy [28,29] and in vitro IgG antibodies are capable of blocking mast cell and basophil mediators released during allergic reactions [30]. If we had focused our study on the most common molecules, Phl p 1, 4, 5, 6 and 2, we would have achieved a reduction in the number of profiles which would ensure that these molecules would be present when administering immunotherapy, and would therefore have achieved the therapeutic goal for most of our population.…”

Developments in allergen‐specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen‐specific immunoglobulin E and T cell reactivity

“…Treatment for periods of 2 years or longer was found to be more effective than the treatment for shorter periods (e.g. 1 year) [42,43]. In the case of sublingual immunotherapy, it is even necessary to administer the allergen extracts on a daily basis for long periods [44].…”

Passive Immunization with Allergen-Specific Antibodies

“…Interestingly, SIT-induced IgG antibodies do not need to recognize exactly the same epitopes as those which are recognized by IgE. In fact, it has been shown that also IgG induced against new epitopes can block IgE binding as long as these antibodies occupy parts of the IgE epitopes or cause steric inhibition of IgE binding (Pree et al 2007;Gadermaier et al 2010a). It should be also stated at this point that the ability of a ''blocking antibody'' to (Visco et al 1996;Flicker et al 2002;Jylha et al 2009;Padavattan et al 2009).…”