Down-Regulation of Human Basophil IgE and FCεRIα Surface Densities and Mediator Release by Anti-IgE-Infusions Is Reversible In Vitro and In Vivo

Abstract

Abstract Previously, infusions of an anti-IgE mAb (rhumAb-E25) in subjects decreased serum IgE levels, basophil IgE and FcεRIα surface density, and polyclonal anti-IgE and Ag-induced basophil histamine release responses. We hypothesized that these effects would be reversed in vivo by discontinuation of infusions and in vitro by exposing basophils to IgE. Subjects received rhumAb-E25 biweekly for 46 wk. Blood samples taken 0–52 wk after rhumAb-E25 were analyzed for serum IgE and basophil expression of IgE, FcεRIα, and CD32. Basophil numbers were unaffected by infusions. Eight weeks after infusions, free IgE levels rose in vivo but did not reach baseline. Basophil IgE and FcεRIα rose in parallel with free IgE while CD32 was stable. FcεRI densities, measured by acid elution, returned to 80% of baseline, whereas histamine release responses returned to baseline. Basophils cultured with or without IgE or IgG were analyzed for expression of IgE, FcεRIα, and CD32. By 7 days with IgE, expression of IgE and FcεRIα rose significantly, whereas cultures without IgE declined. IgE culture did not effect CD32. IgG culture did not effect expression of any marker. The present results strongly suggest that free IgE levels regulate FcεRIα expression on basophils.