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KMID : 0311120160570061412
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Yonsei Medical Journal
2016 Volume.57 No. 6 p.1412 ~ p.1419
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Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation
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Hong Jung-Yeon
Bae Jong-Hwan
Lee Kyung-Eun
Kim Mi-Na
Kim Min-Hee
Kang Hyun-Jung
Park Eun-Hye
Yoo Kyung-Sook
Jeong Se-Kyoo
Kim Kyung-Won
Kim Kyu-Earn
Sohn Myung-Hyun
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Abstract
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Purpose: High-affinity receptor I (FcεRI) on mast cells and basophils plays a key role in the immunoglobulin E (IgE)-mediated type I hypersensitivity mediated by allergen cross-linking of the specific IgE-FcεRI complex. Thus, prevention of IgE binding to FcεRI on these cells is an effective therapy for allergic disease. We have developed a strategy to disrupt IgE binding to FcεRI using an antibody targeting FcεRIα.
Materials and Methods: Fab fragment antibodies, which lack the Fc domain, with high affinity and specificity for FcεRIα and effective inhibitory activity against IgE-FcεRI binding were screened. IgE-induced histamine, β-hexosaminidase and Ca2+ release in basophils were determined by ELISA. A B6.Cg-Fcer1atm1Knt Tg(FCER1A)1Bhk/J mouse model of passive cutaneous anaphylaxis (PCA) was used to examine the inhibitory effect of NPB311 on allergic skin inflammation.
Results: NPB311 exhibited high affinity to human FcεRIα (KD=4 nM) and inhibited histamine, β-hexosaminidase and Ca2+ release in a concentration-dependent manner in hFcεRI-expressing cells. In hFcεRIα-expressing mice, dye leakage was higher in the PCA group than in controls, but decreased after NPB311 treatment. NPB311 could form a complex with FcεRIα and inhibit the release of inflammation mediators.
Conclusion: Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.
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KEYWORD
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Immunoglobulin E (IgE), high-affinity IgE receptor I (FcεRI), Fab fragment, antibody affinity, passive cutaneous anaphylaxis
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