Mechanisms of allergy and clinical immunology
Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge

https://doi.org/10.1016/j.jaci.2009.09.012Get rights and content

Background

Omalizumab treatment suppresses FcεRI expression faster on blood basophils than skin mast cells.

Objective

We used omalizumab to elucidate the relative contributions of basophil versus mast cell FcεRI activation in a nasal allergen challenge (NAC) model.

Methods

Eighteen subjects with cat allergy 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 prostaglandin D2 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 (midstudy 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 midstudy NAC compared with baseline (74% decrease; P = .001). In addition, these subjects demonstrated significant decreases in mean combined nasal symptom scores (50% decrease; P = .007) and total sneeze counts (59% decrease; P = .01) by midstudy NAC relative to baseline NAC. In contrast, measures of mast cell response (SPTT and nasal lavage prostaglandin D2) 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.

Conclusion

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.

Section snippets

Study subjects

Adult subjects between 18 and 50 years of age with a history of cat allergy were recruited by advertising from the greater Baltimore area. Informed consent was obtained via a protocol approved by the Johns Hopkins Hospital Institutional Review Board and the National Institute of Allergy and Infectious Diseases' Data Safety Monitoring Boards. Subjects met the following inclusion criteria for enrollment: a clinical history of cat-induced allergic rhinitis for at least 2 years with or without mild

Subject characteristics

Of the 18 enrolled subjects, 2 of the 14 subjects in the active treatment groups relocated before completion of all NACs. No significant differences were present between baseline characteristics in the 12 active and 4 placebo subjects who completed the study (Table I) or between the initial 14 enrolled subjects in the active group and the placebo group. Data for the 12 subjects on active treatment and the 4 subjects on placebo treatment who completed all 3 study NACs and procedures are reported

Discussion

In this study, we demonstrate a refined kinetics of serum and cellular changes by omalizumab. The expected ∼80% reduction in both basophil surface IgE and FcεRI expression in subjects 10 days after receiving omalizumab followed the expected decline in IgE (>90% in free IgE by day 3). Of note, significant, but modest reductions in cat allergen–induced BHR occurred as early as day 3 at the 0.1 BAU/mL dose (20% decline) and by day 18 at the 1 BAU/mL dose (35% decline) compared with greater

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S.S.S. and B.S.B. received support as Cosner Scholars in Translational Research from Johns Hopkins University. This work was supported by Asthma and Allergic Disease Research Centers grant U19AI070345 from the National Institutes of Health.

Disclosure of potential conflict of interest: S. S. Saini has served as a consultant for and has received research support from Genentech and Novartis. M. C. Liu has served as a consultant for the Novartis Advisory Board and has received research support from Pfizer, Centocor, and Novartis. D. W. MacGlashan Jr has received research support from the National Institutes of Health. The rest of the authors have declared that they have no conflict of interest.

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