Conversion of grass pollen allergen-specific human IgE into a protective IgG1 antibody (original) (raw)
Related papers
Journal of Allergy and Clinical Immunology, 1997
Bet v 1 and homologous proteins represent major allergens for almost 95% of patients allergic to tree pollen and approximately 70% of those allergic to fruits and vegetables. As yet, no continuous (sequential) IgE epitopes have been determined for Bet v 1, and evidence has accumulated that Bet v 1 IgE epitopes belong to the conformational (discontinuous) type. A panel of 85 mouse monoclonal anti-Bet v 1 antibodies was raised as a tool with which to study the interaction of human IgE antibodies with Bet v 1. The epitopes of selected monoclonal antibodies (mAbs) were characterized by mapping with synthetic overlapping peptides and by cross-competition experiments. Cross-reactivity of Bet v 1-specific mAbs with tree and plant food allergens was investigated by Western blotting. The influence of Bet v 1-specific mAbs on the IgE-Bet v 1 interaction was studied by competition assays with immobilized purified recombinant Bet v 1 and by basophil histamine release experiments. Antibodies that increased the IgE binding to Bet v 1 up to fivefold could be defined, whereas others inhibited IgE binding to Bet v 1 up to 99% and competed with the Bet v 1-induced histamine release from patients' basophils. The activity of the enhancing antibodies is interpreted as a stabilization of Bet v 1 states/IgE epitopes, which are either more accessible for certain IgE antibodies or are recognized with higher affinity. Those mAbs that competed with the Bet v 1-IgE interaction, if humanized or produced as recombinant antibody fragments, might be considered as potential tools for local allergy therapy.
Clinical & Experimental Allergy, 1999
Background Although allergen immunotherapy has been established as a treatment of type I allergy back in 1911, until now the underlying mechanisms have not been fully understood, nor are there any parameters which would allow one to monitor an ongoing treatment or to assess therapeutic success in the meantime. Objective We wanted to define allergen-specific parameters that change due to treatment in correlation with the clinical outcome. Methods We conducted a controlled study with grass pollen-allergic children and compared allergen-specific antibody titres before and 1 year after the onset of immunotherapy in contrast with untreated allergic and healthy children. Two recombinant forms of the major allergen group V of Phleum pratense (Phl p 5) served as model allergens. Results No change in IgE levels and no significant reduction of skin prick test (SPT) reactivity were seen. On the other hand, a significant reduction of symptom scores in the treated group and a significant rise in allergen-specific IgG1, IgG2 and IgG4 due to the treatment could be observed, but in neither case could we establish a correlation between the increasing amounts of the single antibody classes and the reduction of symptom scores. But most interestingly, when comparing the ratio of IgG4 to IgG1 with the symtom scores, we found significant correlations. Nevertheless, treated allergic patients still differ considerably from healthy controls as nonatopics have hardly any measurable allergen-specific IgG antibodies and no IgE antibodies at all. Conclusion The ratio of IgG4 to IgG1 can serve as a valuable parameter that allows us to assess the success of immunotherapy already 1 year after the onset. The increase of specific IgG1 in relation to IgG4 during treatment reflects a possible influence of this subclass on the induction of tolerance towards allergens.
NOVEL TREATMENT STRATEGIES AND REGULATION OF IgE-MEDIATED ALLERGIC
2008
Allergic symptoms such as rhinoconjunctivitis, asthma or gastrointestinal symptoms, triggered by inhaled or ingested allergens cross-linking allergen-specific IgE on mast cells or basophils, are defined as IgE-mediated allergy. The major allergens from birch pollen (Bet v 1) and cat dander (Fel d 1) are two common allergens eliciting allergic disease. Allergenspecific immunotherapy (SIT) is the only curative treatment for IgE-mediated allergy. It is long-lasting and involves repeated injections of crude allergen extracts. Successful SIT modifies a number of allergen-associated immunological responses. SIT has been shown to induce IL-10 producing regulatory T-cells (Treg), allergen-specific T-and B-cell anergy as well as blocking antibodies. Although effective, SIT is associated with a risk for treatment side effects. This has led to the development of novel treatment strategies, such as modified recombinant allergens with reduced allergenicity (hypoallergens) and new means of antigen delivery. The general aim of this thesis is to investigate regulation of allergic immune responses and how novel strategies for SIT affect those responses.
Guideline on allergen-specific immunotherapy in IgE-mediated allergic diseases
Allergo Journal International, 2014
e present guideline (S2k) on allergen-speci c immunotherapy (AIT) was established by the German, Austrian and Swiss professional associations for allergy in consensus with the scienti c specialist societies and professional associations in the elds of otolaryngology, dermatology and venereology, pediatric and adolescent medicine, pneumology as well as a German patient organization (German All ergy and Asthma Association; Deutscher Allergie-und Asthmabund, DAAB) according to the criteria of the Association of the Scienti c Medical Societies in Germany (Arbeitsgemeinscha der Wissenscha lichen Medizinischen Fachgesellscha en, AWMF).
Past, presence and future of allergen immunotherapy vaccines
Allergy
Allergen-specific immunotherapy (AIT) is an allergen-specific form of treatment for patients suffering from immunoglobulin E (IgE)-associated allergy; the most common and important immunologically mediated hypersensitivity disease. AIT is based on the administration of the disease-causing allergen with the goal to induce a protective immunity consisting of allergen-specific blocking IgG antibodies and alterations of the cellular immune response so that the patient can tolerate allergen contact.
Allergen
Allergies mediated by immunoglobulin E (IgE) are the most common immunological hypersensitivity diseases. The prevalence has been continuously increasing in recent decades, and more than 25% of the population is currently affected. Symptoms of allergies can be observed in the skin and respiratory and gastrointestinal tracts, and systemic manifestations include anaphylactic shock. If an allergy is not properly diagnosed and treated, it tends to progress to a severe and chronic debilitating disease. Understanding the mechanisms by which the immune system induces and controls allergic inflammation depends on knowing the structure of several allergens and identifying epitopes, which are critical for the design of new strategies for treating allergies. Strategies for immunotherapy will be reviewed. Allergen-specific immunotherapy has been used for nearly a century and remains one of the few antigen-specific treatments for inflammatory diseases. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem, including the use of modified allergens, synthetic peptides as vaccines, and alternative strategies for blocking IgE, will be discussed.
Journal of Allergy and Clinical Immunology, 2001
Objective: We sought to establish an in vitro molecular model for the interaction of human FcεRI, IgE, and the corresponding allergen and to identify monoclonal anti-human IgE antibodies with a therapeutic profile different from previously established anti-IgE antibodies. Methods: Human FcεRI α chain, a human monoclonal allergen-specific IgE antibody (chimeric Bip 1), and the corresponding allergen, the major birch pollen allergen Bet v 1, were produced as recombinant proteins and analyzed by means of circular dichroism and native overlays, respectively. Using this molecular model, as well as negative stain immunoelectron microscopic analysis, and in vitro cultivated human basophils, we characterized mouse anti-human IgE antibodies. Results: We established a molecular model for the interaction of human IgE with FcεRI. Using this molecular model, we identified a nonanaphylactic anti-human IgE antibody fragment (Fab12), which blocked the IgE-FcεRI interaction and reacted with effector cell-bound IgE. Conclusion: Fab12 represents a candidate molecule for therapy of atopy and asthma because it can be used for the depletion of circulating IgE antibodies, as well as for the depletion of IgEbearing cells. (J Allergy Clin Immunol 2001;108:409-16.)
Depigmented Allergoids Reveal New Epitopes with Capacity to Induce IgG Blocking Antibodies
BioMed Research International, 2013
Background. The synthesis of allergen-specific blocking IgGs that interact with IgE after allergen immunotherapy (SIT) has been related to clinical efficacy. The objectives were to investigate the epitope specificity of IgG-antibodies induced by depigmented-polymerized (Dpg-Pol) allergoids and unmodified allergen extracts, and examine IgE-blocking activity of induced IgG-antibodies.Methods. Rabbits were immunized with native and Dpg-Pol extracts of birch pollen, and serum samples were obtained. Recognition of linear IgG-epitopes of Bet v 1 and Bet v 2 and the capacity of these IgG-antibodies to block binding of human-IgE was determined.Results. Serum from rabbits immunized with native extracts recognised 11 linear epitopes from Bet v 1, while that from Dpg-Pol-immunized animals recognised 8. For Bet v 2, 8 epitopes were recognized by IgG from native immunized animals, and 9 from Dpg-Pol immunized one. Dpg-Pol and native immunized serum did not always recognise the same epitopes, but...