Abstract
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.
Original language | English |
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Pages (from-to) | 533-539 |
Number of pages | 7 |
Journal | International Immunopharmacology |
Volume | 10 |
Issue number | 4 |
DOIs | |
State | Published - 04 2010 |
Externally published | Yes |
Keywords
- Allergen trapping
- Allergy
- Anti-IgE
- Basophils
- In vitro reconstitution
- Omalizumab