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J Allergy Clin Immunol. 2004 Aug;114(2):321-7.

Inhibition of allergen-specific IgE reactivity by a human Ig Fcgamma-Fcepsilon bifunctional fusion protein.

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  • 1Hart and Louis Lyon Laboratory, Division of Clinical Immunology and Allergy, Department of Medicine, University of California Los Angeles School of Medicine, CA 90095-1680, USA.

Abstract

BACKGROUND:

Coaggregating FcepsilonRI with FcgammaRII receptors holds great potential for treatment of IgE-mediated disease by inhibiting FcepsilonRI signaling. We have previously shown that an Fcgamma-Fcepsilon fusion protein, human IgG-IgE Fc fusion protein (GE2), could inhibit FcepsilonRI-mediated mediator releases in vitro and in vivo.

OBJECTIVE:

We sought to test whether GE2 was capable of blocking mediator release from FcepsilonRI cells sensitized with IgE in vivo or in vitro before exposure to GE2, a critical feature for GE2 to be clinically applicable.

METHODS:

GE2 was tested for its ability to inhibit Fel d 1-induced mediator release from human blood basophils from subjects with cat allergy, human lung-derived mast cells, human FcepsilonRIalpha transgenic mice sensitized with human cat allergic serum, and rhesus monkeys naturally allergic to the dust mite Dermatophagoides farinae.

RESULTS:

Basophils from subjects with cat allergy and lung mast cells degranulate when challenged with Fel d 1 and anti-IgE, respectively. GE2 itself did not induce mediator release but strongly blocked this Fel d 1- and anti-IgE-driven mediator release. GE2 was able to block Fel d 1-driven passive cutaneous anaphylaxis at skin sites sensitized with human serum from subjects with cat allergy in human FcepsilonRIalpha transgenic mice, but by itself, GE2 did not induce a passive cutaneous anaphylaxis reaction. Finally, GE2 markedly inhibited skin test reactivity to D farinae in monkeys naturally allergic to this allergen, with complete inhibition being observed at 125 ng.

CONCLUSION:

GE2 is able to successfully compete for FcepsilonRs and FcgammaRs on cells presensitized in vitro and in vivo and lead to inhibition of IgE-mediated reactivity through coaggregation of FcepsilonRI with FcgammaRII.

PMID:
15316510
[PubMed - indexed for MEDLINE]
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