Sublingual immunotherapy for peanut allergy: clinical and immunologic evidence of desensitization

Abstract

Background: There are no treatments currently available for peanut allergy. Sublingual immunotherapy (SLIT) is a novel approach to the treatment of peanut allergy.

Objective: We sought to investigate the safety, clinical effectiveness, and immunologic changes with SLIT in children with peanut allergy.

Methods: In this double-blind, placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge.

Results: Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median, 1,710 vs 85 mg; P = .011). Mechanistic studies demonstrated a decrease in skin prick test wheal size (P = .020) and decreased basophil responsiveness after stimulation with 10(-2) μg/mL (P = .009) and 10(-3) μg/mL (P = .009) of peanut. Peanut-specific IgE levels increased over the initial 4 months (P = .002) and then steadily decreased over the remaining 8 months (P = .003), whereas peanut-specific IgG4 levels increased during the 12 months (P = .014). Lastly, IL-5 levels decreased after 12 months (P = .015). No statistically significant changes were found in IL-13 levels, the percentage of regulatory T cells, or IL-10 and IFN-γ production.

Conclusion: Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy, with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance.

Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Figures

Figure 1

DBPCFC after 12 months of SLIT or placebo. [A] When challenged to 2500 mg peanut protein, peanut SLIT subjects demonstrate an increased reaction threshold. Boxes represent interquartile range with a line at the median. Bars represent min and max values. * indicates p=0.011. [B] Association of DBPCFC outcomes with peanut-IgE from the day of challenge for active treatment. ** indicates p=0.043.

Figure 2

Titrated skin prick testing at baseline and after 12 months of peanut SLIT or placebo. After 12 months, peanut SLIT results in a decreased wheal size to peanut skin prick test. Boxes represent interquartile range with a line at the median. Bars represent min and max values. * indicates p=0.020.

Figure 3

Percent of CD63+ activated basophils at baseline and after 12 months of peanut SLIT or placebo. After 12 months, peanut SLIT results in a decreased percent of activated basophils when stimulated with 10−2 and 10−3 mcg/ml of crude peanut extract. Clear boxes - baseline; shaded boxes - 12 month. Boxes represent interquartile range with a line at the median. Bars represent min and max values. * indicates p=0.009, **indicates p=0.009.

Figure 4

Levels of peanut-specific immunoglobulins at baseline and after 12 months of peanut SLIT or placebo. [A] After 12 months, peanut SLIT results in an increase in peanut IgE over 4 months, followed by a decrease over the subsequent 8 months. * indicates p=0.002, ** indicates p=0.003. [B] After 12 months, peanut results in an increase in peanut IgG4. *** indicates p=0.014. Boxes represent interquartile range with a line at the median. Bars represent min and max values.

Figure 5

Cytokine secretion after stimulation with crude peanut extract at baseline and after 12 months of peanut SLIT or placebo. [A] After 12 months, peanut SLIT results in a decrease in IL-5 secretion. * indicates p=0.015. [B] After 12 months, a decrease in IL-13 secretion was found in both peanut SLIT and placebo. Boxes represent interquartile range with a line at the median. Bars represent min and max values.

Figure 6

Percent of T regulatory cells at baseline and after 12 months of peanut SLIT or placebo. Although an increase in TRegs was seen after 12 months of peanut SLIT, this did not reach significance. Boxes represent interquartile range with a line at the median. Bars represent the min and max values.