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

UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
Christopher Kepley, Associate Professor (Creator)
The University of North Carolina at Greensboro (UNCG )
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Abstract: Background: Coaggregating FceRI with FcgRII receptors holds great potential for treatment of IgE-mediated disease by inhibiting FceRI signaling. We have previously shown that an Fcg-Fce fusion protein, human IgG-IgE Fc fusion protein (GE2), could inhibit FceRI-mediated mediator releases in vitro and in vivo. Objective: We sought to test whether GE2 was capable of blocking mediator release from FceRI 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 FceRIa 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 FceRIa 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 FceRs and FcgRs on cells presensitized in vitro and in vivo and lead to inhibition of IgE-mediated reactivity through coaggregation of FceRI with FcgRII.

Additional Information

Journal of Allergy and Clinical Immunology 2004; 114(2):321-7.
Language: English
Date: 2004
Allergen, IgE, FceRI, anaphylaxis, fusion protein, immunotherapy, degranulation, mast cells, basophils, transgenic mouse

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