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Oral exposure to Mal d 1 affects the immune response in patients with birch pollen allergy - 27/12/12

Doi : 10.1016/j.jaci.2012.06.039 
Marija Geroldinger-Simic, MD a, Tamar Kinaciyan, MD b, Birgit Nagl, BMA a, Ursula Baumgartner-Durchschlag, PhD c, Hans Huber, PhD c, Christof Ebner, MD d, Jonas Lidholm, PhD e, Detlef Bartel, PhD f, Stefan Vieths, PhD f, Beatrice Jahn-Schmid, PhD a, Barbara Bohle, PhD a, g,
a Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria 
b Department of Dermatology, Division of Immunology, Allergy and Infectious Diseases (DIAID), Medical University of Vienna, Vienna, Austria 
c Biomay AG, Vienna, Austria 
d Allergy Clinic Reumannplatz, Vienna, Austria 
e Thermo Fisher Scientific, Uppsala, Sweden 
f Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany 
g Christian Doppler Laboratory for Immunomodulation, Medical University of Vienna, Vienna, Austria 

Corresponding author: Barbara Bohle, PhD, Medical University of Vienna, Department of Pathophysiology and Allergy Research, Waehringer Guertel 18-20, AKH-3Q, A-1090 Vienna, Austria.

Abstract

Background

Antibodies and T cells specific for the major birch pollen allergen Bet v 1 cross-react with structurally related food allergens, such as Mal d 1 in apple.

Objective

We sought to evaluate the effects of oral uptake of Mal d 1 on the allergen-specific immune response in patients with birch pollen allergy.

Methods

Patients received 50 μg of rBet v 1 sublingually on 2 consecutive days outside of the birch pollen season. One year later, equal amounts of rMal d 1 were administered. Blood samples were collected before and after oral exposure, as well as before and after the intermediate birch pollen season. Allergen-specific IgE levels were determined by using ImmunoCAP. Proliferation of allergen-stimulated PBMCs was assessed, as well as the expression of IL-5, IL-13, IL-10, IFN-γ, and forkhead box protein 3 (Foxp3) in isolated T cells (real-time PCR). Allergen-specific T-cell lines were analyzed for epitope recognition.

Results

Orally administered Bet v 1 transiently reduced Bet v 1–specific serum IgE levels, as well as Bet v 1– and Mal d 1–induced T-cell proliferation, and enhanced the expression of IL-5, IL-10, and Foxp3. Orally applied Mal d 1 significantly decreased Bet v 1– and Mal d 1–specific IgE levels and induced IL-5 and IL-10 but no Foxp3 expression. In contrast to Bet v 1, Mal d 1 triggered IFN-γ production and T cells with a different epitope repertoire. Inhalation of birch pollen significantly enhanced allergen-specific IgE levels, T-cell proliferation, and IL-5, IL-10, IL-13, and Foxp3 expression.

Conclusion

Two sublingual administrations of 50 μg of Mal d 1 were well tolerated and induced transient immune responses seen during peripheral tolerance development. Thus recombinant Mal d 1 might be suitable and relevant for sublingual treatment of birch pollen–related apple allergy.

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Key words : Birch pollen allergy, food allergy, oral allergy syndrome, Bet v 1, Mal d 1, IgE, T cells

Abbreviations used : aa, cpm, Foxp3, GMP, ISAC, ISU, OAS, SLIT, TCL, TT


Esquema


 Supported by the Austrian Science Fund, project SFB-F1807-B13; the Christian Doppler Research Association; and Biomay AG, Vienna, Austria.
 Disclosure of potential conflict of interest: H. Huber is employed by Biomay AG. J. Lidholm is employed by Thermo Fischer Scientific. S. Vieths has consultant arrangements with the Food Allergy Resource and Research Program, the Institute for Product Quality, and Fresenius Academy; is employed by Johann Wolfgang Goethe-Universität; has provided expert testimony for the Medical University of Vienna; has received grants from Monsanto Company and Pioneer Hi-Bred International; has received payment for lectures from Deutsche Dermatologische Gesellschaft, the Spanish Society of Allergy and Clinical Immunology, Westdeutsche Arbeitsgemeinschaft fur Padiatrische Pneumologie and Allergologie e. V., Gesellschaft fur Padiatrische Allergologie und Umweltmedizin, and the American Academy of Asthma, Allergy & Immunology; has received royalties from Schattauer Allergologie Handbuch and Elsevier Nahrungsmittelallergie und Intoleranzen; and has received travel expenses from the German Research Foundation, the Federal Institute for Risk Assessment, the Austrian Society for Allergology and Immunology, the French Society of Allergology, the European Directorate for the Quality of Medicines and Health Care, the European Academy of Allergy and Clinical Immunology, the World Allergy Organization, the Technical University of Munich, Deutscher Allergie und Asthmabund, Association Monegasque pour le Perfectionnement des Connaissances des Medecins, and the Federal Office of Consumer Protection and Food Safety. B. Jahn-Schmid receives research support from the Austrian National Bank and the Austrian Science Foundation. B. Bohle receives research support from the Austrian Science Fund and the Christian Doppler Laboratory. The rest of the authors declare that they have no relevant conflicts of interest.


© 2012  American Academy of Allergy, Asthma & Immunology. Publicado por Elsevier Masson SAS. Todos los derechos reservados.
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