Immunotherapy with partially purified and standardized tree pollen extracts

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.

Section: Discussionmentioning

confidence: 99%

“…Both forms of therapy were shown to be equally effective in an extensive analysis published in 1988 [6,7,8]. However, a study published 2 years earlier had indicated that a mixture of birch-alder-hazel pollen seemed to be more effective in reducing symptoms than birch pollen extract alone [9].…”

Section: Introductionmentioning

confidence: 99%

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

Gadermaier

Flicker

Aberer

et al. 2009

“…Second, rBet v 1 was found to inhibit the majority of IgE reactivity to pollen allergens from trees of the order Fagales (alder, hazel, hornbeam) and plant-derived food in patients with birch pollen-related oral allergy syndrome [47, 118]. Third, it has been shown that immunotherapy with birch pollen extract was effective in treating allergies not only to birch, but also to pollens of trees of the Fagales order and to birch-related plant foods [154,155,156,157]. Fourth, it has been demonstrated that patients who reacted exclusively with Bet v 1 had a better clinical outcome when treated with birch pollen extract than patients reacting also with other allergens [158].…”

Section: Rbet V 1 As a Diagnostic Marker Allergen To Identify Genuinementioning

confidence: 99%

Transition from a Botanical to a Molecular Classification in Tree Pollen Allergy: Implications for Diagnosis and Therapy

Mothes¹,

Horak

Valenta³

2004

Tree pollens are among the most important allergen sources. Allergic cross-reactivity to pollens of trees from various plant orders has so far been classified according to botanical relationships. In this context, cross-reactivities to pollens of trees of the Fagales order (birch, alder, hazel, hornbeam, oak, chestnut), fruits and vegetables, between pollens of the Scrophulariales (olive, ash, plantain, privet, lilac) and pollens of the Coniferales (cedar, cypress, pine) are well established. The application of molecular biology methods for allergen characterization has revealed the molecular nature of many important tree pollen allergens. We review the spectrum of tree pollen allergens and propose a classification of tree pollen and related allergies based on major allergen molecules instead of botanical relationships among the allergenic sources. This molecular classification suggests the major birch pollen allergen, Bet v 1 as a marker for Fagales pollen and related plant food allergies, the major olive pollen allergen, Ole e 1, as a possible marker for Scrophulariales pollen allergy and the cedar allergens, Cry j 1 and Cry j 2, as potential markers for allergy to Coniferales pollens. We exemplify for Fagales pollen allergy and Bet v 1 that major marker allergens are diagnostic tools to determine the disease-eliciting allergen source. Information obtained by diagnostic testing with marker allergens will be important for the appropriate selection of patients for allergen-specific forms of therapy.

“…Since Bet v 1 and Bet v 2 bind more tree pollen–specific IgE than any other pollen allergen from hazel, oak, birch, alder or hornbeam, they appear to be the most allergenic pollen proteins from these trees. Together, these two allergens harbor most of the IgE epitopes of the Fagales pollen allergens [52], indicating that these birch pollen allergens alone may be effective in diagnosing and treating Fagales pollen allergen [53, 54, 55]. Bet v 3 and Bet v 4 have been identified as calcium–binding proteins [56, 57].…”

Section: Non–anaphylactic Forms Of the Major Birch Pollen Allergen Bmentioning

confidence: 99%

Genetically Engineered Plant Allergens with Reduced Anaphylactic Activity

Singh

Weerd

Bhalla³

1999

Allergy immunotherapy is based on the administration of increasing amounts of the disease–eliciting allergens in order to yield allergen–specific non–responsiveness. Success of this therapy is associated with modulation of the immune response to allergenic molecules at the level of T–helper cells and the induction of blocking antibodies. The extracts used for immunotherapy are highly heterogenous preparations from natural sources and contain additional components, mostly proteins which are not well defined. Recombinant DNA technology offers novel tools for production of pure and well–characterised allergens for specific immunotherapy. However, high IgE reactivity of pure recombinant allergens is associated with an increased risk of potentially life–threatening anaphylactic reactions. A major improvement in allergen–specific immunotherapy may be achieved by using genetically engineered recombinant allergens with reduced anaphylactic activity. Recently the site– directed mutagenesis technique has been applied successfully to produce variants of major grass, birch and oilseed rape allergens with reduced IgE reactivity but retained T–cell reactivity. These modified allergens with reduced anaphylactic potential are novel candidates for safer and more effective allergen–specific immunotherapy.