title: Birch pollen immunotherapy inhibits anaphylaxis to the cross-reactive apple allergen Mal d 1 in mice.
abstract: Cross-reactive apple allergy is a common co-morbidity of birch pollen allergy, caused by the presence of a Bet v 1 homologue allergen in apple, Mal d 1. Treatment of tree pollen hay fever by immunotherapy is well established, but its effect on the accompanying apple allergy is debated.
  
  
  
  To establish a mouse model of birch pollen induced cross-reactivity to Mal d 1 and investigate the effect of birch pollen immunotherapy on the cross-reactivity to Mal d 1.
  
  
  
  Respiratory allergy was induced in Balb/c mice by intraperitoneal exposure to alum-adsorbed birch pollen extract (BPE) in combination with short or prolonged intranasal exposure to BPE. To evaluate the response to Mal d 1, mice were exposed intraperitoneally to Mal d 1. Immunoglobulin responses and cytokine production by splenocytes were measured by ELISA. Allergic symptoms were evaluated by measuring airway hyper-reactivity and hypothermia as a surrogate marker for anaphylaxis. Immunotherapy was performed subcutaneously with alum-adsorbed BPE.
  
  
  
  Mice exposed to BPE develop cross-reactive IgE to Mal d 1. Early after exposure to BPE, this response is still weak and does not yet translate into anaphylaxis. Interestingly, later re-challenge with BPE increased cross-reactivity to a level where Mal d 1 exposure induced anaphylaxis. Cross-sensitization can also be induced by systemic Mal d 1 exposure. Birch pollen immunotherapy significantly reduced the anaphylactic response of mice to Mal d 1.
  
  
  
  A mouse model mimicking birch pollen induced cross-reactivity to Mal d 1 was successfully established. In this model, birch pollen immunotherapy significantly ameliorated the anaphylaxis induced by Mal d 1. Our experimental data suggest that boosting of Mal d 1 recognizing immunoglobulins by BP SCIT is important for the amelioration of apple allergy in human.
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. lara.utsch@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Utsch
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Logiantara
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Wallner
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Hofer
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.|Department of Otorhinolaryngology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: van Ree
authors.affiliation: Department of Experimental Immunology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. l.s.vanrijt@amc.uva.nl.
authors.forename: L S
authors.initials: LS
authors.lastname: van Rijt
mesh_terms: D000485:Allergens / Q000276:immunology*; D000707:Anaphylaxis / Q000097:blood / Q000276:immunology*; D000818:Animals; D052179:Antigens, Plant / Q000276:immunology*; D029662:Betula / Q000009:adverse effects*; D015415:Biomarkers; D003429:Cross Reactions / Q000276:immunology*; D003888:Desensitization, Immunologic; D004195:Disease Models, Animal; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007165:Immunosuppression Therapy; D027845:Malus / Q000009:adverse effects*; D051379:Mice; D010940:Plant Proteins / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D015415:Biomarkers; C095551:MALD1 protein, Malus domestica; D010940:Plant Proteins; D007073:Immunoglobulin E
keywords: Bet v 1; Mal d 1; apple allergy; cross-reactivity; immunotherapy