Omalizumab treatment downregulates dendritic cell FcεRI expression

Abstract

Background Dendritic cells (DCs) are potent antigen-presenting cells that express FcεRI, the high-affinity IgE receptor. Although the downregulation of basophil FcεRI during anti-IgE therapy with omalizumab is well documented, its effect on FcεRI expression by DCs has not been reported. Objective We hypothesized that IgE regulates surface FcεRI expression by DCs in vivo and that, consequently, anti-IgE therapy decreases FcεRI expression by DCs. Methods In a randomized, double-blind, placebo-controlled clinical trial 24 subjects (16 receiving omalizumab and 8 receiving placebo) with seasonal allergic rhinitis received the study drug on days 0 and 28. Serial blood samples drawn on days 0, 7, 14, 28, and 42 were analyzed for precursor DC1 (pDC1) and pDC2 surface expression of FcεRIα by using flow cytometry. Results Omalizumab caused a significant decrease in surface FcεRI expression at all time points examined in both the pDC1 and pDC2 subsets. No significant change was seen with placebo. The maximum decrease in FcεRI expression in the omalizumab group was 52% and 83%, respectively, for the pDC1 and pDC2 subsets. The decrease in FcεRI expression by both pDC subsets correlated with the decrease in serum-free IgE and was of a similar magnitude to that found in basophils. A 10-fold decrease in IgE corresponded to a 42% and 54% decrease in surface FcεRI expression by the pDC1 and pDC2 subsets, respectively. Conclusion These results demonstrate that anti-IgE therapy causes a rapid decrease in DC surface FcεRI expression and establish that IgE is an important regulator of FcεRI expression by DCs.