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. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
RCT Entities:
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. Copyright (c) 2010 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
Authors: Michelle A Gill; Andrew H Liu; Agustin Calatroni; Rebecca Z Krouse; Baomei Shao; Allison Schiltz; James E Gern; Alkis Togias; William W Busse Journal: J Allergy Clin Immunol Date: 2017-09-01 Impact factor: 10.793
Authors: P A Frischmeyer-Guerrerio; A L Guerrerio; K L Chichester; A P Bieneman; R A Hamilton; R A Wood; J T Schroeder Journal: Clin Exp Allergy Date: 2010-09-05 Impact factor: 5.018
Authors: Pamela A Frischmeyer-Guerrerio; Corinne A Keet; Anthony L Guerrerio; Kristin L Chichester; Anja P Bieneman; Robert G Hamilton; Robert A Wood; John T Schroeder Journal: Clin Immunol Date: 2014-08-27 Impact factor: 3.969