Down-regulation of human basophil IgE and FC epsilon RI alpha surface densities and mediator release by anti-IgE-infusions is reversible in vitro andin vivo

Previously, infusions of an anti-IgE mAb (rhumAb-E25) in subjects decreased serum IgE levels, basophil IgE and Fc epsilon RI alpha surface density, an d polyclonal anti-IgE and Ag-induced basophil histamine release responses, We hypothesized that these effects would be reversed in vivo by discontinua tion of infusions and in vitro bg exposing basophils to IgE, Subjects recei ved rhumAb-E25 biweekly for 46 wk. Blood samples taken 0-52 wk after rhum-A b-E25 were analyzed for serum IgE and basophil expression of IgE, Fc epsilo n RI alpha, and CD32, Basophil numbers were unaffected by infusions. Eight weeks after infusions, free IgE levels rose in vivo but did not reach basel ine. Basophil IgE and Fc epsilon RI alpha rose in parallel Kith free IgE wh ile CD32 was stable, Fc epsilon RI densities, measured by. acid elution, re turned to 80% of baseline, whereas histamine release responses returned to baseline. Basophils cultured with or without IgE or IgG were analyzed for e xpression of IgE Fc epsilon RI alpha, and CD32. By 7 days with IgE, express ion of IgE and Fc epsilon RI alpha rose significantly, whereas cultures wit hout IgE declined. IgE culture did not effect CD32. Ige culture did not eff ect expression of any marker. The present results strongly suggest that fre e IgE levels regulate Fc epsilon RI alpha expression on basophils.