Down-Regulation of FcεRI Expression on Human Basophils during in Vivo Treatment of Atopic Patients with Anti-IgE Antibody

Treatment of allergic disease by decreasing circulating IgE with anti-IgE Abs is currently under clinical study. Based on previous unrelated studies, it appeared likely that FcεRI expression on basophils and mast cells might also be regulated by levels of circulating IgE Ab. Therefore, the expression of IgE and FcεRI on human basophils was examined in 15 subjects receiving humanized anti-IgE mAb intravenously. Treatment with the anti-IgE mAb decreased free IgE levels to 1 % of pretreatment levels and also resulted in a marked down-regulation of FcεRI on basophils. Median pretreatment densities of FcεRI were ≈220,000 receptors per basophil and after 3 mo of treatment, the densities had decreased to a median of 8,300 receptors per basophil. Flow cytometric studies, conducted in parallel, showed similar results and also showed in a subset of 3 donors that receptors decreased with a t_1/2 of approximately 3 days. The responsiveness of the cells to IgE-mediated stimulation using anti-IgE Ab was marginally decreased (≈40%) while the response of the same cells to stimulation with dust mite Ag, Dermatophagoides farinae, was reduced by ≈90%. One possible explanation for these results is that FcεRI density is directly or indirectly regulated by plasma-free IgE levels.