title: Oral exposure to Mal d 1 affects the immune response in patients with birch pollen allergy.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Marija
authors.initials: M
authors.lastname: Geroldinger-Simic
authors.forename: Tamar
authors.initials: T
authors.lastname: Kinaciyan
authors.forename: Birgit
authors.initials: B
authors.lastname: Nagl
authors.forename: Ursula
authors.initials: U
authors.lastname: Baumgartner-Durchschlag
authors.forename: Hans
authors.initials: H
authors.lastname: Huber
authors.forename: Christof
authors.initials: C
authors.lastname: Ebner
authors.forename: Jonas
authors.initials: J
authors.lastname: Lidholm
authors.forename: Detlef
authors.initials: D
authors.lastname: Bartel
authors.forename: Stefan
authors.initials: S
authors.lastname: Vieths
authors.forename: Beatrice
authors.initials: B
authors.lastname: Jahn-Schmid
authors.forename: Barbara
authors.initials: B
authors.lastname: Bohle
mesh_terms: D000284:Administration, Oral; D000328:Adult; D052179:Antigens, Plant / Q000008:administration & dosage / Q000276:immunology*; D029662:Betula / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D052179:Antigens, Plant; D016207:Cytokines; D000939:Epitopes; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C095551:MALD1 protein, Malus domestica; D010940:Plant Proteins; D007073:Immunoglobulin E