title: Efficacy of birch-pollen immunotherapy on cross-reactive food allergy confirmed by skin tests and double-blind food challenges.
abstract: BACKGROUND
  The effect of birch-pollen immunotherapy (IT) on cross-reactive food allergies is controversial.
  
  
  OBJECTIVE
  The aim of this study was to investigate the effect of birch-pollen IT on apple allergy and to evaluate recombinant allergens and double-blind placebo-controlled food challenges (DBPCFCs) as monitoring tools.
  
  
  METHODS
  Twenty-five adult birch-pollen- and apple-allergic patients were randomly divided into two groups, either receiving birch-pollen IT or symptomatic drugs only. IgE and IgG4 antibodies against birch pollen, apple, natural Bet v 1 and Mal d 1 were measured. In addition, skin prick tests (SPT) were performed using recombinant Bet v 1 (rBet v 1) and Mal d 1 (rMal d 1). Clinical outcome was evaluated by DBPCFC. CD4(+)CD25(+) regulatory T cells (Tregs) were isolated from peripheral blood and tested in functional assays.
  
  
  RESULTS
  Birch-pollen IT resulted in a significant decrease of SPT reactivity for rBet v 1 (30-fold) and rMal d 1 (10-fold) already after 3 months. IgG4 antibodies were potently induced against Bet v 1, displaying cross-reactivity to Mal d 1. Visual analogue scale scores decreased >10-fold in 9/13 patients of the IT group, with three patients converting to negative. In the control group, no decrease was observed. Birch-pollen IT did not lead to detectable changes in the number or function of the CD4(+)CD25(+) Tregs.
  
  
  CONCLUSIONS
  This trial supports the claims that birch-pollen IT also decreases allergy to foods containing Bet v 1-homologous allergens. Recombinant allergens and DBPCFCs have proven to be useful tools for monitoring the effect of birch-pollen IT on linked food allergies.
authors.affiliation: Department of Dermatology/Allergology, University Medical Center Utrecht, Utrecht, The Netherlands. S.Bolhaar@azu.nl
authors.forename: S T H P
authors.initials: ST
authors.lastname: Bolhaar
authors.forename: M M
authors.initials: MM
authors.lastname: Tiemessen
authors.forename: L
authors.initials: L
authors.lastname: Zuidmeer
authors.forename: A
authors.initials: A
authors.lastname: van Leeuwen
authors.forename: K
authors.initials: K
authors.lastname: Hoffmann-Sommergruber
authors.forename: C A F M
authors.initials: CA
authors.lastname: Bruijnzeel-Koomen
authors.forename: L S
authors.initials: LS
authors.lastname: Taams
authors.forename: E F
authors.initials: EF
authors.lastname: Knol
authors.forename: E
authors.initials: E
authors.lastname: van Hoffen
authors.forename: R
authors.initials: R
authors.lastname: van Ree
authors.forename: A C
authors.initials: AC
authors.lastname: Knulst
mesh_terms: D000328:Adult; D000485:Allergens; D052179:Antigens, Plant; D029662:Betula; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003429:Cross Reactions; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D005502:Food / Q000009:adverse effects; D005512:Food Hypersensitivity / Q000175:diagnosis / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007159:Immunologic Tests; D008213:Lymphocyte Activation; D008297:Male; D027845:Malus; D010940:Plant Proteins; D011058:Pollen; D011994:Recombinant Proteins; D012882:Skin Tests
chemical_list: D000485:Allergens; D052179:Antigens, Plant; C095551:MALD1 protein, Malus domestica; D010940:Plant Proteins; D011994:Recombinant Proteins