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

• Published in: Journal of allergy and clinical immunology Vol. 125; no. 4; pp. 902 - 908.e7
• Main Authors: Zaidi, Asifa K, Saini, Sarbjit S, MacGlashan, Donald W
• Format: Journal Article
• Language: English
• Published: 01.04.2010
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2009.12.996

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 FceRI in basophils differs among subjects. This observation raised the possibility that the stoichiometry of FcRb/FceRIa 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 FcRb and FceRIa. Method - Syk, FceRIa, and FcRb 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 FcRb/FceRIa 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 FceRI a and b subunits in basophils is influenced by factors extrinsic to the cell.