Antibody to FcεRIα Suppresses Immunoglobulin E Binding to High-Affinity Receptor I in Allergic Inflammation
Authors
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
Citation
YONSEI MEDICAL JOURNAL, Vol.57(6) : 1412-1419, 2016
Fab fragment ; Immunoglobulin E (IgE) ; antibody affinity ; high-affinity IgE receptor I (FcεRI) ; passive cutaneous anaphylaxis
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-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.