Kinetics of mast cell, basophil, and oral food challenge responses in omalizumab-treated adults with peanut allergy

Abstract

Background: Monoclonal antibodies directed at IgE demonstrate clinical efficacy in subjects with peanut allergy, but previous studies have not addressed the kinetics of the clinical response or the role of mast cells and basophils in the food-induced allergic response.

Objective: We sought to determine the kinetics of the clinical response to omalizumab and whether clinical improvement is associated with either mast cell or basophil suppression.

Methods: Subjects with peanut allergy were treated with omalizumab for 6 months and assessed for clinical and cellular responses. At baseline, subjects had a double-blind, placebo-controlled oral food challenge (OFC), skin prick test titration (SPTT), and basophil histamine release (BHR) to peanut. BHR was repeated at week 2 and then weekly until it decreased to less than 20% of baseline values. The OFCs and SPTTs were repeated after the BHR reduction (or at week 8 if BHR did not decrease) and again at 6 months.

Results: Fourteen subjects enrolled in the study. At the second food challenge, there was a significant increase in the threshold dose of peanut inducing allergic symptoms (80 to 6500 mg, P < .01). Peanut-induced BHR was either completely suppressed (n = 5) or 10-fold more allergen was required to induce maximal BHR (n = 9), and SPTT responses were not significantly changed from baseline. After 6 months of omalizumab, further changes in the OFC threshold dose or BHR were not observed, but a significant suppression in SPTTs was identified.

Conclusions: The clinical response to omalizumab occurs early in treatment when the basophil, but not the mast cell, is suppressed, supporting a role for the basophil in acute food reactions.

FIG 1

Overall study design. *OFC2 and SPTT at this time point occurred when Pn-BHR AUC values were less than 20% of baseline values or at week 8.

FIG 2

OFC results. A, Results for all subjects. B, Results for 6 subjects who completed all 3 OFCs and did not reach 10,000 mg. The median threshold dose for each time point is indicated by a red bar. *P < .05, see text for details. Dashed lines indicate group A subjects; solid lines indicate group B subjects.

FIG 3

Occurrence of allergic symptoms during OFCs for the 10 subjects who completed all 3 food challenges. Values are the percentages of subjects who reported symptoms in each organ system. There were no significant differences between OFC1, OFC2, and OFC3. CV, Cardiovascular; GI, gastrointestinal; Resp., respiratory.

FIG 4

Mean skin prick test results ± SEMs. *P < .05 compared with OFC1.

FIG 5

Peanut-induced BHR across 8 concentrations of allergen at OFCs. A, Group A. B, Group B. Values are means ± SEMs.