National Tsing Hua University Institutional Repository:Accumulated immune complexes of IgE and omalizumab trap allergens in an in vitro model
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    National Tsing Hua University Institutional Repository > 生命科學院  > 生命科學系 > 期刊論文 >  Accumulated immune complexes of IgE and omalizumab trap allergens in an in vitro model


    题名: Accumulated immune complexes of IgE and omalizumab trap allergens in an in vitro model
    作者: Chuan-Long Hsu;Yu-Yu Shiung;Bai-Ling Lin;Hwan-You Chang;Tse Wen Chang
    教師: 張晃猷
    日期: 2010
    出版者: Elsevier
    關聯: International Immunopharmacology,Elsevier,Volume 10,Issue 4,April 2010,Pages 533-539
    关键词: Anti-IgE
    Allergen trapping
    In vitro reconstitution
    摘要: The best understood mechanisms of omalizumab are that it neutralizes free IgE and down-regulates high-affinity IgE.Fc receptors (FcεRI) on basophils and mast cells. It has been proposed that since complexes of IgE and omalizumab are accumulated to 5–10 times the basal levels of IgE, they may trap incoming allergens, contributing to omalizumab's effectiveness. In order to investigate the ability of IgE:omalizumab complexes in trapping allergens and inhibiting basophil activation in an in vitro reconstitution model, the ability of IgE:omalizumab complexes to tie up antigen and hence inhibit (a) antigen binding to IgE bound by FcεRI, and (b) antigen-mediated activation of basophils, was examined. The free IgE was prepared by mixing different proportions of antigen-nonspecific IgE secreted by U266 cells and antigen-specific IgE, SE44 IgE, which recognizes a synthetic 15 a.a. peptide, R15K. The antigen was (R15K)8-ova, i.e. ovalbumin conjugated with an average of 8 copies of R15K per molecule. The solid-phase FcεRI was a recombinant protein representing the extracellular portion of the α chain of the FcεRI receptor complex. The model FcεRI+ basophilic cell line was RBL.SX-38, a rat basophilic leukemic line transfected with the genes for α, β and γ subunits of human FcεRI. The results showed that the IgE:omalizumab complexes trapped increasing amounts of antigen with increasing (a) concentration of IgE, (b) proportion of antigen-specific IgE in total IgE, and (c) concentration of total immune complexes. Such trapping decreased the antigen-induced activation of FcεRI+ cells that had been pulsed with antigen-specific IgE, resulting in decreased mediator release. These results suggest that the rapidly accumulated IgE:omalizumab complexes in omalizumab-treated patients can capture allergens and consequently contribute to the pharmacological effects of omalizumab.
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