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J Allergy Clin Immunol. 2015 May;135(5):1283-92. doi: 10.1016/j.jaci.2014.11.010. Epub 2014 Dec 24.

Suppression of the immunologic response to peanut during immunotherapy is often transient.

Author information

1
Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
2
Department of Pediatrics, Division of Allergy, Immunology and Infectious Diseases, University of Medicine and Dentistry of New Jersey, Newark, NJ.
3
Department of Pediatrics, Division of Gastroenterology and Nutrition, Johns Hopkins University School of Medicine, Baltimore, Md.
4
Department of Medicine, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md.
5
Department of Pediatrics, Division of Allergy and Immunology, Johns Hopkins University School of Medicine, Baltimore, Md. Electronic address: pamela.guerrerio@nih.gov.

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.

KEYWORDS:

Peanut allergy; basophil activation; dendritic cells; food allergy; oral immunotherapy; sublingual immunotherapy; sustained unresponsiveness

PMID:
25542883
PMCID:
PMC4426213
DOI:
10.1016/j.jaci.2014.11.010
[Indexed for MEDLINE]
Free PMC Article

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