Frequent occurrence of T cell–mediated late reactions revealed by atopy patch testing with hypoallergenic rBet v 1 fragments

• Published in: Journal of allergy and clinical immunology 2016-02, Vol.137 (2), p.601-609.e8
• Main Authors: Campana, Raffaela, PhD, Moritz, Katharina, MD, Marth, Katharina, MD, Neubauer, Angela, PhD, Huber, Hans, PhD, Henning, Rainer, PhD, Blatt, Katharina, PhD, Hoermann, Gregor, MD, PhD, Brodie, Tess M., PhD, Kaider, Alexandra, MSc, Valent, Peter, MD, Sallusto, Federica, PhD, Wöhrl, Stefan, MD, MSc, Valenta, Rudolf, MD
• Format: Article
• Language: English
• Subjects: Adult; allergen; Allergens - immunology; Allergies; Allergy; Allergy and Immunology; Antigens, Plant - immunology; Asthma; atopy patch testing; Betula - adverse effects; birch pollen allergy; CCR4; Clinical trials; cutaneous lymphocyte antigen; Cytokines; Cytokines - biosynthesis; Dermatitis, Atopic - diagnosis; Dermatitis, Atopic - immunology; Dermatitis, Atopic - metabolism; Female; Histamine Release; Humans; Hypersensitivity, Delayed - diagnosis; Hypersensitivity, Delayed - immunology; Hypersensitivity, Delayed - metabolism; Hypersensitivity, Immediate - diagnosis; Hypersensitivity, Immediate - immunology; Hypersensitivity, Immediate - metabolism; Inflammation; late-phase reaction; Lymphocyte Activation - immunology; Lymphocytes; Male; Patch Tests; Pollen - immunology; Quality of life; rBet v 1; rBet v 1 fragments; recombinant hypoallergens; Rhinitis, Allergic, Seasonal - diagnosis; Rhinitis, Allergic, Seasonal - immunology; specific immunotherapy; Studies; T-Cell Antigen Receptor Specificity - immunology; T-cell proliferation; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Young Adult
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2015.08.042

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. Conclusion 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.