PMID- 20132969
OWN - NLM
STAT- MEDLINE
DCOM- 20100426
LR  - 20220408
IS  - 1097-6825 (Electronic)
IS  - 0091-6749 (Linking)
VI  - 125
IP  - 4
DP  - 2010 Apr
TI  - Decreases in human dendritic cell-dependent T(H)2-like responses after acute in 
      vivo IgE neutralization.
PG  - 896-901.e6
LID - 10.1016/j.jaci.2009.10.021 [doi]
AB  - BACKGROUND: Dendritic cells (DCs) and other professional antigen-presenting cells 
      express a variant of the high-affinity IgE receptor known as alphagamma(2), 
      which, on the basis of in vitro findings, has long been implicated to function in 
      facilitating allergen uptake and presentation to T(H) cells. OBJECTIVES: To use 
      omalizumab as an in vivo tool to neutralize IgE binding to circulating dendritic 
      cells and to assess whether this results in altered DC-dependent T-cell 
      responsiveness to allergen ex vivo. METHODS: Subjects with cat allergy were 
      enrolled in a 3.5-month, double blind, randomized (3.5:1), placebo-controlled 
      trial of omalizumab using standard dosing for allergic asthma. Blood plasmacytoid 
      and myeloid DCs were assessed at baseline and posttreatment for expression of 
      surface IgE, FcepsilonRIalpha, and induction of CD4(+)T-cell proliferation and 
      cytokine responses to cat allergen. RESULTS: IgE expression on plasmacytoid and 
      myeloid DCs from omalizumab-treated subjects (n = 12) decreased by > or =95% 
      posttreatment (P = .0005), whereas FcepsilonRIalpha expression decreased by 66% 
      and 48%, respectively (P = .0005). Cat allergen-induced proliferation in 
      DC/T-cell cocultures observed at baseline was suppressed approximately 20% to 40% 
      postomalizumab treatment (P = .001). Multiplexing for cytokines in plasmacytoid 
      DC/T-cell cocultures also showed decreases in IL-5, IL-13, and IL-10 (P < .05), 
      whereas IL-2 and IFN-gamma were unaltered or slightly increased. These changes 
      were not evident in placebo-control subjects (n = 4). CONCLUSION: IgE likely 
      facilitates allergen presentation by dendritic cells in vivo and is also 
      important in regulating DC-dependent T-cell cytokines during effector phases of 
      allergic disease.
CI  - Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by 
      Mosby, Inc. All rights reserved.
FAU - Schroeder, John T
AU  - Schroeder JT
AD  - Division of Allergy and Clinical Immunology at the Johns Hopkins Asthma and 
      Allergy Center, Department of Medicine, Johns Hopkins University, Baltimore, Md, 
      USA. schray@jhmi.edu
FAU - Bieneman, Anja P
AU  - Bieneman AP
FAU - Chichester, Kristin L
AU  - Chichester KL
FAU - Hamilton, Robert G
AU  - Hamilton RG
FAU - Xiao, Huiqing
AU  - Xiao H
FAU - Saini, Sarbjit S
AU  - Saini SS
FAU - Liu, Mark C
AU  - Liu MC
LA  - eng
GR  - U19 AI070345/AI/NIAID NIH HHS/United States
GR  - U19AI070345-01/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, N.I.H., Extramural
DEP - 20100204
PL  - United States
TA  - J Allergy Clin Immunol
JT  - The Journal of allergy and clinical immunology
JID - 1275002
RN  - 0 (Allergens)
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Cytokines)
RN  - 0 (Receptors, IgE)
RN  - 2P471X1Z11 (Omalizumab)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Allergens/immunology
MH  - Animals
MH  - Antibodies, Anti-Idiotypic
MH  - Antibodies, Monoclonal/administration & dosage/*immunology
MH  - Antibodies, Monoclonal, Humanized
MH  - Antibodies, Neutralizing/administration & dosage/*immunology
MH  - Antigen Presentation
MH  - CD4-Positive T-Lymphocytes/immunology
MH  - Cats
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Dendritic Cells/*immunology
MH  - Double-Blind Method
MH  - Humans
MH  - Hypersensitivity/drug therapy/immunology
MH  - Immunoglobulin E/immunology/*metabolism
MH  - Middle Aged
MH  - Omalizumab
MH  - Receptors, IgE/metabolism
MH  - Th2 Cells/*immunology
MH  - Young Adult
EDAT- 2010/02/06 06:00
MHDA- 2010/04/27 06:00
CRDT- 2010/02/06 06:00
PHST- 2009/05/14 00:00 [received]
PHST- 2009/10/13 00:00 [revised]
PHST- 2009/10/20 00:00 [accepted]
PHST- 2010/02/06 06:00 [entrez]
PHST- 2010/02/06 06:00 [pubmed]
PHST- 2010/04/27 06:00 [medline]
AID - S0091-6749(09)01549-8 [pii]
AID - 10.1016/j.jaci.2009.10.021 [doi]
PST - ppublish
SO  - J Allergy Clin Immunol. 2010 Apr;125(4):896-901.e6. doi: 
      10.1016/j.jaci.2009.10.021. Epub 2010 Feb 4.