A chimeric human-cat fusion protein blocks cat-induced allergy.

The Hart and Louise Lyon Laboratory, Division of Clinical Immunology/Allergy, Department of Medicine, UCLA School of Medicine, 10833 Le Conte Avenue, Los Angeles, California 90095-1680, USA.
Nature Medicine (Impact Factor: 28.05). 05/2005; 11(4):446-9. DOI: 10.1038/nm1219
Source: PubMed

ABSTRACT Animal allergens are an important cause of asthma and allergic rhinitis. We designed and tested a chimeric human-cat fusion protein composed of a truncated human IgG Fcgamma1 and the major cat allergen Fel d1, as a proof of concept for a new approach to allergy immunotherapy. This Fcgamma-Fel d1 protein induced dose-dependent inhibition of Fel d1-driven IgE-mediated histamine release from cat-allergic donors' basophils and sensitized human cord blood-derived mast cells. Such inhibition was associated with altered Syk and ERK signaling. The Fcgamma-Fel d1 protein also blocked in vivo reactivity in FcepsilonRIalpha transgenic mice passively sensitized with human IgE antibody to cat and in Balb/c mice actively sensitized against Fel d1. The Fcgamma-Fel d1 protein alone did not induce mediator release. Chimeric human Fcgamma-allergen fusion proteins may provide a new therapeutic platform for the immune-based therapy of allergic disease.

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