Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge

Abstract

BACKGROUND Omalizumab treatment suppresses FcεRI expression faster on blood basophils than skin mast cells. OBJECTIVE We utilized omalizumab to elucidate the relative contributions of basophil versus mast cell FcεRI activation in a nasal allergen challenge (NAC) model. METHODS 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). RESULTS 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. CONCLUSIONS 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.

Randomized Trial of Omalizumab (Anti-IgE) for Asthma in Inner-City Children

“…[27][28][29] Another potential approach to the same goal would be to focus the use of omalizumab on preventing seasonal peaks in asthma exacerbations; this would require studies examining a short, seasonal course of treatment in those at highest risk. The fact that the maximum effect of omalizumab occurred within 1 month, rather than 3 to 4 months, as previously reported, 19,[39][40][41] supports the potential benefit of this treatment approach.…”

Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives

“…In another study including 24 patients with allergen-induced rhinitis, free IgE levels decreased by 96% and FcεRI expression on basophils decreased by 75% after omalizumab treatment [53]. Reduction in surface IgE and FcεRI expression was also demonstrated in subjects with cat allergy [54]. Moreover, in a recent study of 15 asthmatics who received omalizumab for 12 weeks, basophil FcεRI expression was decreased by 96% while at the same time IL-4, IL-8 and IL-13 FcεRI-mediated production decreased [55].…”

Immunotherapy in allergy and cellular tests

“…At the same time, this evidence appears quite paradoxical respect to previous reports, showing a basophil desensitization following omalizumab immunotherapy. 50 Certainly, immunotherapy may affect basophils directly and their expression of surface markers, such as CD63, CD193, CD203c, CD69, CD164, usually upregulated during cellular activation, may be significantly modified during treatment. Despite to the many difficulties in interpretating BAT, 23 this consideration prompted researchers to evaluate BAT as a promising tool during immunotherapy follow up.…”