Regulation of Syk kinase and FcR beta 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 Fc is an element of RI in basophils differs among subjects. This observation raised the possibility that the stoichiometry of FcR beta/Fc epsilon RI alpha 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 FcR beta and Fc is an element of RI alpha. Method: Syk, Fc is an element of RI alpha, and FcR beta 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 FcR beta/Fc is an element of R1 alpha 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 Fc is an element of RI alpha and beta subunits in basophils is influenced by factors extrinsic to the cell. (J Allergy Clin Immunol 2010;125:902-8.)