Journal
CLINICAL AND EXPERIMENTAL ALLERGY
Volume 42, Issue 8, Pages 1197-1205Publisher
WILEY
DOI: 10.1111/j.1365-2222.2012.04028.x
Keywords
basophil anergy; CD203c; CD63; desensitization; human basophils; oral immunotherapy; peanut allergy
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Funding
- Food Allergy & Anaphylaxis Network
- Food Allergy Project
- Gerber Foundation
- NIH [1 R01-AI06874-01A1, 1 UL1 RR024128-01, R03-AI079544, 5T32-AI007062-32]
- Dorothy & Frank Robins Family
- National Peanut Board
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Background In Westernized countries, over 1% of the population is allergic to peanuts or tree nuts, which carries a risk of severe allergic reactions. Several studies support the efficacy of peanut oral immunotherapy (OIT) for reducing the clinical sensitivity of affected individuals; however, the mechanisms of this effect are still being characterized. One mechanism that may contribute is the suppression of effector cells, such as basophils. Basophil anergy has been characterized in vitro as a pathway-specific hyporesponsiveness; however, this has not been demonstrated to occur in vivo. Objective To evaluate the hypothesis that basophil anergy occurs in vivo due to chronic allergen exposure in the setting of a clinical oral immunotherapy trial. Methods Samples of peripheral blood were obtained from subjects during a placebo-controlled clinical trial of peanut OIT. Basophil reactivity to in vitro stimulation with peanut allergen and controls was assessed by the upregulation of activation markers, CD63 and CD203c, measured by flow cytometry. Results The upregulation of CD63 following stimulation of the IgE receptor, either specifically with peanut allergen or non-specifically with anti-IgE antibody, was strongly suppressed by active OIT. However, OIT did not significantly suppress this response in basophils stimulated by the distinct fMLP receptor pathway. In the subset of subjects with egg sensitization, active peanut OIT also suppressed CD63 upregulation in response to stimulation with egg allergen. Allergen OIT also suppressed the upregulation of CD203c including in response to stimulation with IL-3 alone. Conclusion Peanut OIT induces a hyporesponsive state in basophils that is consistent with pathway-specific anergy previously described in vitro. This suggests the hypothesis that effector cell anergy could contribute to clinical desensitization.
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