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Cor a 1–reactive T cells and IgE are predominantly cross-reactive to Bet v 1 in patients with birch pollen–associated food allergy to hazelnut - 29/04/13

Doi : 10.1016/j.jaci.2012.10.037 
Claudia Hofmann, MSc a, Stephan Scheurer, PhD b, Kathrin Rost a, Edith Graulich a, Annette Jamin b, Kay Foetisch, PhD b, Joachim Saloga, MD a, Stefan Vieths, PhD b, Kerstin Steinbrink, MD a, , Henric S. Adler, PhD a,
a Department of Dermatology, University Medical Center of the Johannes Gutenberg-Universität, Mainz, Germany 
b Paul-Ehrlich-Institut, Langen, Germany 

Corresponding author: Kerstin Steinbrink, MD, University Medical Center Mainz, Johannes Gutenberg-Universität Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.Henric S. Adler, PhD, University Medical Center Mainz, Johannes-Gutenberg-Universität Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany.

Abstract

Background

IgE- and T-cell cross-reactivity contribute to the birch pollen–food syndrome.

Objectives

We performed a comprehensive analysis of T-cell cross-reactivity in primary cell cultures, facilitating the identification of allergen-specific T-cell subpopulations from individual patients.

Methods

Patients with birch pollen allergy and associated food allergy to hazelnuts, carrots, or both were analyzed for IgE cross-reactivity, T-cell responses, and T-cell cross-reactivity to recombinant Bet v 1.0101 (Bet v 1; birch), Cor a 1.0401 (Cor a 1; hazelnut), and Dau c 1.0104 (Dau c 1; carrot). A novel flow cytometry–based method using a 2-step staining process with fluorescent dyes was established to identify subpopulations of cross-reactive T cells.

Results

IgE-binding inhibition tests of individual sera revealed that the vast majority of Cor a 1–reactive IgE was cross-reactive to Bet v 1, whereas Bet v 1–reactive IgE was only partially inhibited by preincubation with Cor a 1. Primary stimulation of T cells with Bet v 1 or Cor a 1 resulted in a significant increase in specific responses to Cor a 1 or Bet v 1 after secondary stimulation, respectively, indicating T-cell cross-reactivity between birch and hazelnut allergens in all patients of the study cohort. Preactivation with Dau c 1 induced less pronounced effects. A novel flow cytometry–based proliferation assay identified a predominant Cor a 1/Bet v 1–cross-reactive T-cell subpopulation within highly Bet v 1/Cor a 1–responsive T cells.

Conclusion

Analysis of primary allergen-specific T cells combined with flow cytometry–based proliferation assays facilitates investigation of allergen-specific T-cell subpopulations in subjects and might be helpful to evaluate the effect of birch-specific immunotherapy on pollen-associated food allergies.

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Key words : T-cell cross-reactivity, birch pollen allergy, hazelnut, carrot, food allergy, Bet v 1, Cor a 1, Dau c 1, oral allergy syndrome, type I allergy, IgE, pathogenesis-related proteins

Abbreviations used : Bet v 1, CFSE, Cor a 1, Dau c 1, DC, OVA, SI, SIT


Plan


 Supported by the German Research Foundation (Transregio 52/TPA7, DFG STE791/4-5, STE791/5-1) to K.S. and the Foundation Rhineland-Palatinate to (K.S. and H.S.A.) and intramural grants (to K.S.).
 Disclosure of potential conflict of interest: J. Saloga has been supported by one or more grants from ALK-Abelló, the Foundation for Innovation (Mainz), and the University of Mainz. S. Vieths has received honoraria from the Food Allergy Resource and Research Program; has received support from the German Federal Ministry of Health, the German Research Foundation (Deutsche Forschungsgemeinschaft, DVG VI 165/6-1 and GVG VI 165/71), the Research Fund of the German Food Industry (Forschungskreis der Ernährungsindustrie, FEI), Monsanto, Pioneer Hi-Bred International, the Food Allergy Research & Resource Program, the European Directorate for the Quality of Medicines and Health Care (EDQM), and the German Federal Ministry for Education and Research; is a member of the Executive Committee of the European Academy of Allergy and Clinical Immunology (EAACI); serves on subcommittees of the International Union of Immunological Societies (IUIS); is a registered expert for the European Agency for the Evaluation of Medicinal Products (EMEA) and the European Pharmacopoeia Commission; is chairman of Technical Committee 275 Working Group 12 “Food Allergens” for CEN (the European Committee for Standardization); and is a member of the Food Allergy Working Group of the Deutsche Gesellschaft für Allergie und Klinische Immunologie (DGAKI). The rest of the authors declare that they have no relevant conflicts of interest.


© 2012  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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