Suppression of the immunologic response to peanut during immunotherapy is often transient.
Abstract
BACKGROUND:
Studies suggest that oral immunotherapy (OIT) and sublingual immunotherapy (SLIT) for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood.
OBJECTIVE:
We sought to generate insights into the mechanisms and duration of suppression of immune responses to peanut during immunotherapy.
METHODS:
Blood was obtained from subjects at baseline and at multiple time points during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included measurement of spontaneous and stimulated basophil activity by using automated fluorometry (histamine) and flow cytometry (activation markers and IL-4), measurement of allergen-induced cytokine expression in dendritic cell (DC)-T-cell cocultures by using multiplexing technology, and measurement of MHC II and costimulatory molecule expression on DCs by using flow cytometry.
RESULTS:
Spontaneous and allergen-induced basophil reactivity (histamine release, CD63 expression, and IL-4 production) were suppressed during dose escalation and after 6 months of maintenance dosing. Peanut- and dust mite-induced expression of TH2 cytokines was reduced in DC-T-cell cocultures during immunotherapy. This was associated with decreased levels of CD40, HLA-DR, and CD86 expression on DCs and increased expression of CD80. These effects were most striking in myeloid DC-T-cell cocultures from subjects receiving OIT. Many markers of immunologic suppression reversed after withdrawal from immunotherapy and in some cases during ongoing maintenance therapy.
CONCLUSION:
OIT and SLIT for peanut allergy induce rapid suppression of basophil effector functions, DC activation, and TH2 cytokine responses during the initial phases of immunotherapy in an antigen-nonspecific manner. Although there was some interindividual variation, in many patients suppression appeared to be temporary.
Published by Elsevier Inc.
KEYWORDS:
Peanut allergy; basophil activation; dendritic cells; food allergy; oral immunotherapy; sublingual immunotherapy; sustained unresponsiveness
- PMID:
- 25542883
- [PubMed – indexed for MEDLINE]
- PMCID:
- PMC4426213
- [Available on 2016-05-01]
LINK TO: Suppression of the immunologic response to peanut during immunotherapy is often transient. J Allergy Clin Immunol. 2015 May;135(5):1283-92.