Omalizumab treatment suppresses FcεRI expression faster on blood basophils than skin mast cells.
We utilized omalizumab to elucidate the relative contributions of basophil versus mast cell FcεRI activation in a nasal allergen challenge (NAC) model.
Eighteen cat-allergic subjects were enrolled in a 3.5-month, double-blind, randomized (3.5:1), placebo-controlled trial of omalizumab using standard dosing. At baseline, subjects underwent NAC with lavage for PGD2 measurement, skin prick test titration (SPTT), and blood sampling for basophil histamine release (BHR) and basophil IgE/FcεRI 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 (mid-study NAC) and at the treatment period’s completion (final NAC).
Subjects treated with omalizumab who completed all NACs (n=12) demonstrated significant mean reduction in BHR to an optimal dose of cat allergen by mid-study NAC as compared to baseline (74% decrease, p=0.001). In addition, these subjects demonstrated significant decreases in mean combined nasal symptom scores (50% decrease, p=0.007) and total sneeze counts (59% decrease, p=0.01) by mid-study NAC relative to baseline NAC. In contrast, measures of mast cell response (SPTT and nasal lavage PGD2) were only significantly reduced by the final NAC. Subjects on placebo (n=4) did not experience a shift in basophil, NAC symptom, or mast cell measures.
Reduction in nasal symptom scores occurred when the basophil, but not mast cell, response was reduced on omalizumab, implicating a role for basophils in the acute NAC response.