The Effect of Omalizumab on Basophil and Mast Cell Responses using an Intranasal Cat Allergen Challenge

Abstract

RATIONALE: Omalizumab treatment suppresses basophil FcɛRI expression faster than skin mast cells. We utilized omalizumab to elucidate the relative contributions of basophil versus mast cell activation in a nasal allergen challenge (NAC) model. METHODS: Eleven cat-allergic subjects were enrolled in a 3.5-month, double-blinded, randomized (3.5:1), placebo-controlled trial of omalizumab using standard allergic asthma dosing. Cat allergen was used for all study procedures. At baseline, subjects underwent NAC-1 with lavage for PGD2 measurement, skin prick test titration (SPTT), and blood sampling for basophil histamine release (BHR) and basophil IgE/IgE-receptor measurements. Basophil studies were repeated at day 3 and then weekly until cat allergen-induced BHR was <20% of baseline or until day 45. Baseline visit procedures were repeated after the BHR reduction (NAC-2) and at the treatment period's completion (NAC-3). RESULTS: In subjects with a >80% reduction in their basophil IgE receptors by day 10 (n = 8), BHR to their optimal dose (0.1 or 1 BAU/mL) of cat allergen was significantly lower by NAC-2 compared to NAC-1 (71% decrease; p = 0.03). Compared to NAC-1, these subjects demonstrated significant decreases in total sneeze counts (59% decrease, p = 0.03) and combined nasal symptom scores (53% decrease, p = 0.02) by NAC-2. In contrast, no significant (p > 0.05) shifts in SPTT or nasal lavage PGD2 were seen until NAC-3. Subjects without a significant change in their basophil IgE receptors (n = 3) had no significant shifts in any outcome. CONCLUSIONS: Reduction in nasal symptom scores occurred when the basophil, but not mast cell, response was reduced. NAC responses appear partially basophil dependent.