Regulation of Syk kinase and FcRbeta expression in human basophils during treatment with omalizumab.

Background: In human basophils from different subjects, maximum IgE-mediated histamine release and the level of Syk protein expression correlate well. Recent studies suggest that in some patients treated with omalizumab, the response to stimulation with anti-IgE antibody increases. In unrelated studies there is also evidence that the composition of FcepsilonRI in basophils differs among subjects. This observation raised the possibility that the stoichiometry of FcRbeta/FcepsilonRIalpha is not fixed to a 1:1 ratio and might be modifiable during changes in the basophil's environment.

Objective: We sought to determine whether treatment with omalizumab results in increases in Syk expression and anti-IgE-mediated histamine release and disproportionately alters the relative presence of FcRbeta and FcepsilonRIalpha.

Method: Syk, FcepsilonRIalpha, and FcRbeta expression was monitored during the treatment of subjects with omalizumab.

Results: Treatment with omalizumab reduced histamine release from peripheral blood leukocytes stimulated with cat allergen in vitro, but histamine release stimulated with anti-IgE antibody increased 2-fold. Expression of Syk increased 1.86-fold. There was no change in the expression of c-Cbl, a signaling element that is sensitive to the presence of IL-3, and no increase in response to formyl-met-leu-phe (tripeptide), a response that also increases in the presence of IL-3. There was a 60% decrease in the FcRbeta/FcepsilonRIalpha ratio in patients treated with omalizumab.

Conclusions: In the context of previous studies, these studies provide support for a proposal that Syk expression is modulated in vivo through an IgE-dependent mechanism and that the ratio of FcepsilonRI alpha and beta subunits in basophils is influenced by factors extrinsic to the cell.