DOWN-REGULATION OF FC-EPSILON-RI EXPRESSION ON HUMAN BASOPHILS DURINGIN-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 Fc epsilon RI expression on basophil s and mast cells might also be regulated by levels of circulating IgE Ab. Therefore, the expression of IgE and Fc epsilon RI on human basoph ils was examined in 15 subjects receiving humanized anti-IgE mAb intra venously. Treatment with the anti-IgE mAb decreased free IgE levels to 1% of pretreatment levels and also resulted in a marked down-regulati on of Fc epsilon RI on basophils, Median pretreatment densities of Fc epsilon RI were approximate to 220,000 receptors per basophil and afte r 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 respons iveness of the cells to IgE-mediated stimulation using anti-IgE Ab was marginally decreased (approximate to 40%) while the response of the s ame cells to stimulation with dust mite Ag, Dermatophagoides farinae, was reduced by approximate to 90%. One possible explanation for these results is that Fc epsilon RI density is directly or indirectly regula ted by plasma-free IgE levels.