Mechanisms of AllergyOmalizumab treatment downregulates dendritic cell FcεRI expression☆
Section snippets
Study design
This analysis was performed as a substudy within a single-center, randomized, double-blind, placebo-controlled clinical trial of 24 subjects (16 receiving omalizumab and 8 receiving placebo) with ragweed-induced seasonal allergic rhinitis conducted from December 2001 to March 2002. Subjects 19 to 50 years old with a minimum 2-year history of ragweed-induced seasonal allergic rhinitis and a serum IgE level of less than 700 IU/mL were enrolled. Subjects with a history of asthma or who were
Clinical study
A clinical trial examining the pharmacodynamics of omalizumab therapy was performed from December 2001 through March 2002 in subjects with ragweed-induced seasonal allergic rhinitis and is described in detail elsewhere.16 Serial blood samples for IgE levels and flow cytometry were analyzed as detailed in the “Methods” section. The median baseline serum IgE level was 250 and 131 ng/mL for the omalizumab and placebo groups, respectively. In the omalizumab group free serum IgE decreased 95% by day
Discussion
In this work we examined FcεRIα expression during a clinical trial of omalizumab and demonstrate that omalizumab treatment is associated with a decrease in cell-surface FcεRI expression in both the pDC1 and pDC2 subsets. Furthermore, we found a correlation between the decrease in DC FcεRI expression and the decrease in IgE in this study population. These results are consistent with the conclusion that this decrease in FcεRI expression occurs as a direct consequence of the reduction in free IgE
Acknowledgements
We thank Dr Mark VanRaden (NIAID) for statistical consultation and Bryan Sandlund (Genentech) for free IgE determinations.
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The clinical trial was supported by a grant from Genentech Inc, South San Francisco, Calif. The dendritic cells analyses were funded by the National Institute of Allergy and Infectious Diseases Division of Intramural Research.