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Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation

 Jung Yeon Hong  ;  Jong-Hwan Bae  ;  Kyung Eun Lee  ;  Mina Kim  ;  Min Hee Kim  ;  Hyun Jung Kang  ;  Eun Hye Park  ;  Kyung Sook Yoo  ;  Se Kyoo Jeong  ;  Kyung Won Kim  ;  Kyu-Earn Kim  ;  Myung Hyun Sohn 
 YONSEI MEDICAL JOURNAL, Vol.57(6) : 1412-1419, 2016 
Journal Title
Issue Date
Allergens ; Animals ; Antibodies, Monoclonal/metabolism ; Antibodies, Monoclonal/pharmacology* ; Basophils/immunology* ; Basophils/metabolism ; Humans ; Hypersensitivity/immunology ; Immunoglobulin E/immunology ; Immunoglobulin E/metabolism* ; Immunoglobulin E/physiology ; Immunoglobulin Fab Fragments/metabolism* ; Inflammation/metabolism ; Mast Cells ; Mice ; Receptors, IgE/immunology* ; Receptors, IgE/metabolism ; Receptors, IgE/physiology
Fab fragment ; Immunoglobulin E (IgE) ; antibody affinity ; high-affinity IgE receptor I (FcεRI) ; passive cutaneous anaphylaxis
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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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kyung Won(김경원) ORCID logo https://orcid.org/0000-0003-4529-6135
Kim, Kyu Earn(김규언)
Sohn, Myung Hyun(손명현) ORCID logo https://orcid.org/0000-0002-2478-487X
Hong, Jung Yeon(홍정연) ORCID logo https://orcid.org/0000-0003-0406-9956
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