Mechanisms of asthma and allergic inflammationOmalizumab-induced reductions in mast cell FcεRI expression and function
Section snippets
Subjects
The 3 subjects in this report had a history of moderately severe perennial allergic rhinitis and provided informed consent to venous blood sampling, skin testing, and skin biopsies per protocols approved by the Johns Hopkins Institutional Review Board. Subjects were participants in a phase I trial of omalizumab, as previously reported, and received omalizumab, 0.03 mg/kg/IU IgE/mL, administered intravenously on a bimonthly basis for 6 months.1., 2. In the first week of dosing, these subjects
Serum IgE levels and basophil FcεRIα
These results have been previously published and are noted here to provide background for the mast cell studies. At baseline, the 3 omalizumab recipients had a mean IgE level of 1037 ± 394 ng/mL (432 ± 164 IU/mL). One week after initiation of omalizumab, subjects had an approximately 99% reduction in free IgE levels that was maintained through day 196 (Fig 1, A). As previously reported,1 these subjects also showed an 88% reduction in basophil surface FcεRIα expression 1 week after initiating
Discussion
In earlier reports we demonstrated a clear relationship between free IgE levels and FcεRI expression on blood basophils in allergic subjects undergoing omalizumab infusion. Furthermore, the decrease in basophil FcεRI expression was accompanied by a decrease in basophil histamine response to allergen challenge.1., 2. Separately, a reduction in mast cell FcεRI expression, function, or both was implicated by the reduction in acute skin test size after several weeks of omalizumab infusion,5 and
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Supported in part by National Institutes of Health grants AI01564 and AI045839.