Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation.
10.3349/ymj.2016.57.6.1412
- Author:
Jung Yeon HONG
1
;
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
Author Information
1. Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea. MHSOHN@yuhs.ac
- Publication Type:Original Article
- Keywords:
Immunoglobulin E (IgE);
high-affinity IgE receptor I (FcεRI);
Fab fragment;
antibody affinity;
passive cutaneous anaphylaxis
- MeSH:
Animals;
Antibodies;
Antibody Affinity;
Basophils;
Enzyme-Linked Immunosorbent Assay;
Histamine;
Humans;
Hypersensitivity, Immediate;
Immunoglobulin E*;
Immunoglobulins*;
Inflammation Mediators;
Inflammation*;
Mast Cells;
Mice;
Passive Cutaneous Anaphylaxis;
Sensitivity and Specificity;
Skin
- From:Yonsei Medical Journal
2016;57(6):1412-1419
- CountryRepublic of Korea
- Language:English
-
Abstract:
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-Fcer1a(tm1Knt) 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.
