title: Frequent occurrence of T cell-mediated late reactions revealed by atopy patch testing with hypoallergenic rBet v 1 fragments.
abstract: BACKGROUND
  Late allergic reactions are common in the course of allergen-specific immunotherapy and even occur with allergy vaccines with reduced IgE reactivity.
  
  
  OBJECTIVE
  We sought to study atopy patch test (APT) reactions and T-cell responses to the recombinant birch pollen allergen Bet v 1 and recombinant hypoallergenic T-cell epitope-containing Bet v 1 fragments in patients with birch pollen allergy with and without atopic dermatitis (AD).
  
  
  METHODS
  A clinical study was conducted in 15 patients with birch pollen allergy with AD (group 1), 5 patients with birch pollen allergy without AD (group 2), 5 allergic patients without birch pollen allergy (group 3), and 5 nonallergic subjects (group 4) by performing skin prick tests and APTs with rBet v 1 and hypoallergenic rBet v 1 fragments. T-cell, cutaneous lymphocyte antigen (CLA)(+) and CCR4(+) T-cell and cytokine responses were studied by thymidine uptake, carboxyfluorescein diacetate succinimidyl ester staining, and Luminex technology, respectively.
  
  
  RESULTS
  rBet v 1 and hypoallergenic rBet v 1 fragments induced APT reactions in not only most of the patients with birch pollen allergy with AD (11/15) but also in most of those without AD (4/5). Patients with birch pollen allergy with AD had higher Bet v 1-specific proliferation of CLA(+) and CCR4(+) T cells compared with patients with birch pollen allergy without AD. There were no differences in Bet v 1-specific CLA(+) and CCR4(+) proliferation and cytokine secretion in patients with and without APT reactions.
  
  
  CONCLUSIONS
  Hypoallergenic rBet v 1 fragments induce T cell-dependent late reactions not only in patients with birch pollen allergy with AD but also in those without AD, which can be determined based on APT results but not based on in vitro parameters.
authors.affiliation: Division of Immunopathology, Department of Pathophysiology, Center of Physiology and Pathophysiology, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria.
authors.forename: Raffaela
authors.initials: R
authors.lastname: Campana
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Moritz
authors.affiliation: Division of Immunopathology, Department of Pathophysiology, Center of Physiology and Pathophysiology, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Marth
authors.affiliation: Biomay AG, Vienna Competence Center, Vienna, Austria.
authors.forename: Angela
authors.initials: A
authors.lastname: Neubauer
authors.affiliation: Biomay AG, Vienna Competence Center, Vienna, Austria.
authors.forename: Hans
authors.initials: H
authors.lastname: Huber
authors.affiliation: Biomay AG, Vienna Competence Center, Vienna, Austria.
authors.forename: Rainer
authors.initials: R
authors.lastname: Henning
authors.affiliation: Division of Hematology and Hemostaseology, Department of Internal Medicine I, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Blatt
authors.affiliation: Department of Laboratory Medicine, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria.
authors.forename: Gregor
authors.initials: G
authors.lastname: Hoermann
authors.affiliation: Cellular Immunology Laboratory, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland.
authors.forename: Tess M
authors.initials: TM
authors.lastname: Brodie
authors.affiliation: Center for Medical Statistics, Informatics and Intelligent Systems, Section for Clinical Biometrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kaider
authors.affiliation: Division of Hematology and Hemostaseology, Department of Internal Medicine I, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Cellular Immunology Laboratory, Institute for Research in Biomedicine, University of Italian Switzerland, Bellinzona, Switzerland.
authors.forename: Federica
authors.initials: F
authors.lastname: Sallusto
authors.affiliation: Division of Immunology, Allergy and Infectious Diseases (DIAID), Department of Dermatology, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wöhrl
authors.affiliation: Division of Immunopathology, Department of Pathophysiology, Center of Physiology and Pathophysiology, Vienna General Hospital (AKH), Medical University of Vienna, Vienna, Austria. Electronic address: rudolf.valenta@meduniwien.ac.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
mesh_terms: D000328:Adult; D000485:Allergens / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology*; D029662:Betula / Q000009:adverse effects; D016207:Cytokines / Q000096:biosynthesis; D003876:Dermatitis, Atopic / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D005260:Female; D006636:Histamine Release; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000175:diagnosis* / Q000276:immunology* / Q000378:metabolism; D006969:Hypersensitivity, Immediate / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D010328:Patch Tests; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000276:immunology; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines
keywords: Allergy; CCR4; T-cell proliferation; allergen; atopy patch testing; birch pollen allergy; cutaneous lymphocyte antigen; late-phase reaction; rBet v 1; rBet v 1 fragments; recombinant hypoallergens; specific immunotherapy