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

John A. Eckman, Patricia M. Sterba, Denise Kelly, Val Alexander, Mark C. Liu, Bruce S. Bochner, Donald W. MacGlashan, Sarbjit S. Saini

Research output: Contribution to journalArticle

Abstract

Background: Omalizumab treatment suppresses Fcε{lunate}RI expression faster on blood basophils than skin mast cells. Objective: We used omalizumab to elucidate the relative contributions of basophil versus mast cell Fcε{lunate}RI 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/Fcε{lunate}RI 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.

Original languageEnglish (US)
Pages (from-to)889-895.e7
JournalJournal of Allergy and Clinical Immunology
Volume125
Issue number4
DOIs
StatePublished - Apr 2010

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Keywords

  • IgE
  • IgE receptors
  • basophil histamine release
  • basophils
  • cat allergy
  • mast cells
  • nasal allergen challenge
  • omalizumab
  • skin prick test titration

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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