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Clinical & Experimental Allergy

Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy

Authors

  • M. Tarzi,

    1. Department of Allergy & Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart & Lung Institute, London, UK,
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  • S. Klunker,

    1. Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland,
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    • 1Current address: Upper Respiratory Medicine, Imperial College London, Faculty of Medicine, National Heart & Lung Institute, London.

  • C. Texier,

    1. Protein Engineering and Research Department, Commissariat a l'Energie Atomique-Saclay, Gif sur Yvette cedex, France, and
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  • A. Verhoef,

    1. Department of Allergy & Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart & Lung Institute, London, UK,
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  • S. O. Stapel,

    1. Protein Engineering and Research Department, Commissariat a l'Energie Atomique-Saclay, Gif sur Yvette cedex, France, and
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  • C. A. Akdis,

    1. Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland,
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  • B. Maillere,

    1. Protein Engineering and Research Department, Commissariat a l'Energie Atomique-Saclay, Gif sur Yvette cedex, France, and
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  • A. B. Kay,

    1. Department of Allergy & Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart & Lung Institute, London, UK,
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  • M. Larché

    1. Department of Allergy & Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart & Lung Institute, London, UK,
    2. Department of Allergy Diagnostics, CLB Sanguin, Amsterdam, Netherlands
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Correspondence:
Mark Larché, Department of Allergy & Clinical Immunology, Imperial College London, Faculty of Medicine, National Heart & Lung Institute, Dovehouse Street, London SW3 6LY, UK.
E-mail: m.larche@imperial.ac.uk

Summary

Background Allergen-derived (T cell epitope) peptides may be safer for immunotherapy than native allergen, as they do not cross-link immunoglobulin (Ig)E. However, HLA polymorphism results in multiple potential epitopes. Synthetic peptides of phospholipase (PL) A2 were selected for a peptide vaccine, on the basis of binding affinity for commonly expressed HLA-DR molecules.

Objective To evaluate treatment with an HLA-DR-based PLA2 peptide vaccine in subjects with mild honeybee allergy in an open, controlled study.

Methods Twelve volunteers with allergy to bee venom received nine intradermal injections of PLA2 peptides, with six untreated subjects serving as controls. Outcome was assessed by the size of the late-phase cutaneous reaction to allergen, peripheral blood mononuclear cell (PBMC) proliferation, cytokine release, and expression of genes associated with immune regulation.

Results Subjects receiving peptides showed a decrease in the magnitude of the late-phase cutaneous reaction to bee venom compared with controls (P=0.03). The proliferation of venom-stimulated PBMCs decreased in treated subjects compared with controls (P=0.01). Peptide treatment reduced the production of IL-13 by PLA2-stimulated PBMCs (P<0.01) and IFN-γ (P<0.01), and increased the production of IL-10 (P=0.02). Transcription of the suppressor of cytokine signalling (Socs)3 gene was significantly increased following therapy. A transient, but modest, increase in allergen-specific IgG was also observed.

Conclusion HLA-DR-based T cell epitopes modify surrogate markers associated with successful immunotherapy and induction of immune regulation, supporting the concept that this form of treatment may be efficacious in human allergic disease.

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