PMID- 27593869
OWN - NLM
STAT- MEDLINE
DCOM- 20170227
LR  - 20181202
IS  - 1976-2437 (Electronic)
IS  - 0513-5796 (Print)
IS  - 0513-5796 (Linking)
VI  - 57
IP  - 6
DP  - 2016 Nov
TI  - Antibody to FcepsilonRIalpha Suppresses Immunoglobulin E Binding to High-Affinity Receptor 
      I in Allergic Inflammation.
PG  - 1412-9
LID - 10.3349/ymj.2016.57.6.1412 [doi]
AB  - PURPOSE: High-affinity receptor I (FcepsilonRI) 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-FcepsilonRI complex. Thus, prevention of IgE 
      binding to FcepsilonRI on these cells is an effective therapy for allergic disease. We 
      have developed a strategy to disrupt IgE binding to FcepsilonRI using an antibody 
      targeting FcepsilonRIalpha. MATERIALS AND METHODS: Fab fragment antibodies, which lack the 
      Fc domain, with high affinity and specificity for FcepsilonRIalpha and effective inhibitory 
      activity against IgE-FcepsilonRI binding were screened. IgE-induced histamine, 
      beta-hexosaminidase and Ca(2)(+) 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 FcepsilonRIalpha (KD=4 
      nM) and inhibited histamine, beta-hexosaminidase and Ca(2)(+) release in a 
      concentration-dependent manner in hFcepsilonRI-expressing cells. In hFcepsilonRIalpha-expressing 
      mice, dye leakage was higher in the PCA group than in controls, but decreased 
      after NPB311 treatment. NPB311 could form a complex with FcepsilonRIalpha and inhibit the 
      release of inflammation mediators. CONCLUSION: Our approach for producing 
      anti-FcepsilonRIalpha Fab fragment antibody NPB311 may enable clinical application to a 
      therapeutic pathway in IgE/FcepsilonRI-mediated diseases.
FAU - Hong, Jung Yeon
AU  - Hong JY
AD  - Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project 
      for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
FAU - Bae, Jong Hwan
AU  - Bae JH
AD  - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
FAU - Lee, Kyung Eun
AU  - Lee KE
AD  - Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project 
      for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
FAU - Kim, Mina
AU  - Kim M
AD  - Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project 
      for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
FAU - Kim, Min Hee
AU  - Kim MH
AD  - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
FAU - Kang, Hyun Jung
AU  - Kang HJ
AD  - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
FAU - Park, Eun Hye
AU  - Park EH
AD  - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
FAU - Yoo, Kyung Sook
AU  - Yoo KS
AD  - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
FAU - Jeong, Se Kyoo
AU  - Jeong SK
AD  - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
FAU - Kim, Kyung Won
AU  - Kim KW
AD  - Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project 
      for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
FAU - Kim, Kyu Earn
AU  - Kim KE
AD  - Department of Pediatrics and Institute of Allergy, Brain Korea 21 PLUS Project 
      for Medical Science, Yonsei University College of Medicine, Seoul, Korea.
FAU - Sohn, Myung Hyun
AU  - Sohn MH
AD  - 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.
LA  - eng
PT  - Journal Article
PL  - Korea (South)
TA  - Yonsei Med J
JT  - Yonsei medical journal
JID - 0414003
RN  - 0 (Allergens)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (FcepsilonRIalpha protein, mouse)
RN  - 0 (Immunoglobulin Fab Fragments)
RN  - 0 (Receptors, IgE)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Allergens
MH  - Animals
MH  - Antibodies, Monoclonal/metabolism/*pharmacology
MH  - Basophils/*immunology/metabolism
MH  - Humans
MH  - Hypersensitivity/immunology
MH  - Immunoglobulin E/immunology/*metabolism/physiology
MH  - Immunoglobulin Fab Fragments/*metabolism
MH  - Inflammation/metabolism
MH  - Mast Cells
MH  - Mice
MH  - Receptors, IgE/*immunology/metabolism/physiology
PMC - PMC5011273
OTO - NOTNLM
OT  - Fab fragment
OT  - Immunoglobulin E (IgE)
OT  - antibody affinity
OT  - high-affinity IgE receptor I (FcepsilonRI)
OT  - passive cutaneous anaphylaxis
COIS- The authors have no financial conflicts of interest.
EDAT- 2016/09/07 06:00
MHDA- 2017/02/28 06:00
PMCR- 2016/11/01
CRDT- 2016/09/06 06:00
PHST- 2016/02/16 00:00 [received]
PHST- 2016/03/21 00:00 [revised]
PHST- 2016/03/24 00:00 [accepted]
PHST- 2016/09/06 06:00 [entrez]
PHST- 2016/09/07 06:00 [pubmed]
PHST- 2017/02/28 06:00 [medline]
PHST- 2016/11/01 00:00 [pmc-release]
AID - 57.1412 [pii]
AID - 10.3349/ymj.2016.57.6.1412 [doi]
PST - ppublish
SO  - Yonsei Med J. 2016 Nov;57(6):1412-9. doi: 10.3349/ymj.2016.57.6.1412.