Decreases in human dendritic cell-dependent TH2-like responses after acute in vivo IgE neutralization

Background: Dendritic cells (DCs) and other professional antigen-presenting cells express a variant of the high-affinity IgE receptor known as alpha gamma(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, Fc is an element of RI alpha, 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 >= 95% posttreatment (P=.0005), whereas Fc is an element of RI alpha expression decreased by 66% and 48%, respectively (P=.0005). Cat allergen induced proliferation in DC/T-cell cocultures observed at baseline was suppressed similar to 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. (J Allergy Clin Immunol 2010;125:896-901.)