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Evidence of pathway‐specific basophil anergy induced by peanut oral immunotherapy in peanut‐allergic children
Author(s) -
Thyagarajan A.,
Jones S. M.,
Calatroni A.,
Pons L.,
Kulis M.,
Woo C. S.,
Kamalakannan M.,
Vickery B. P.,
Scurlock A. M.,
Wesley Burks A.,
Shreffler W. G.
Publication year - 2012
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/j.1365-2222.2012.04028.x
Subject(s) - basophil , immunology , basophil activation , immunoglobulin e , medicine , sensitization , allergen , ex vivo , downregulation and upregulation , population , allergy , in vivo , antibody , biology , microbiology and biotechnology , biochemistry , gene , environmental health
Background In W esternized 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, CD 63 and CD 203c, measured by flow cytometry. Results The upregulation of CD 63 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 CD 63 upregulation in response to stimulation with egg allergen. Allergen OIT also suppressed the upregulation of CD 203c 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.