Effects of omalizumab on basophil and mast cell responses using an intranasal cat allergen challenge.
BACKGROUND
Omalizumab treatment suppresses FcepsilonRI expression faster on blood basophils than skin mast cells.


OBJECTIVE
We used omalizumab to elucidate the relative contributions of basophil versus mast cell FcepsilonRI 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 D(2) measurement, skin prick test titration (SPTT), and blood sampling for basophil histamine release (BHR) and basophil IgE/FcepsilonRI 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 D(2)) 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.
Eckman
John A
JA
Division of Allergy and Clinical Immunology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md, USA.
Sterba
Patricia M
PM
Kelly
Denise
D
Alexander
Val
V
Liu
Mark C
MC
Bochner
Bruce S
BS
Macglashan
Donald W
DW
Saini
Sarbjit S
SS
D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D018926:Anti-Allergic Agents / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001491:Basophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D002415:Cats / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D006636:Histamine Release; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008875:Middle Aged; D009299:Nasal Provocation Tests; D000069444:Omalizumab; D017455:Receptors, IgE / Q000378:metabolism; D012882:Skin Tests; D055815:Young Adult
D000485:Allergens; D018926:Anti-Allergic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D017455:Receptors, IgE; D000069444:Omalizumab