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


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.


CONCLUSIONS
Our approach for producing anti-FcεRIα Fab fragment antibody NPB311 may enable clinical application to a therapeutic pathway in IgE/FcεRI-mediated diseases.
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Jung Yeon
JY
Hong
CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
Jong Hwan
JH
Bae
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Kyung Eun
KE
Lee
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Mina
M
Kim
CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
Min Hee
MH
Kim
CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
Hyun Jung
HJ
Kang
CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
Eun Hye
EH
Park
CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
Kyung Sook
KS
Yoo
CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
Se Kyoo
SK
Jeong
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Kyung Won
KW
Kim
Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
Kyu Earn
KE
Kim
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.
Myung Hyun
MH
Sohn
D000485:Allergens; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000494:pharmacology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008407:Mast Cells; D051379:Mice; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism / Q000502:physiology
D000485:Allergens; D000911:Antibodies, Monoclonal; C579617:FcepsilonRIalpha protein, mouse; D007140:Immunoglobulin Fab Fragments; D017455:Receptors, IgE; D007073:Immunoglobulin E
Fab fragment; Immunoglobulin E (IgE); antibody affinity; high-affinity IgE receptor I (FcεRI); passive cutaneous anaphylaxis