Background-Although promising results have emerged regarding oral and sublingual immunotherapy (OIT and SLIT) for the treatment of peanut allergy, direct comparisons of these approaches are limited.
Background Studies suggest that oral (OIT) and sublingual (SLIT) immunotherapy for food allergy hold promise; however, the immunologic mechanisms underlying these therapies are not well understood. Objective To generate insights into the mechanisms and duration of immunologic suppression to peanut during immunotherapy (IT). Methods Blood was obtained from subjects at baseline and at multiple timepoints during a placebo-controlled trial of peanut OIT and SLIT. Immunologic outcomes included spontaneous and stimulated basophil activity by automated fluorometry (histamine) and flow cytometry (activation markers, IL-4), allergen-induced cytokine expression in dendritic cell (DC)-T cell co-cultures by multiplexing technology, and expression of MHC II and costimulatory molecules on DCs by 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 co-cultures during IT. 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 co-cultures from subjects receiving OIT. Many markers of immunologic suppression reversed following withdrawal from IT, and in some cases during ongoing maintenance therapy. Conclusion OIT and SLIT for peanut allergy induce rapid suppression of basophil effector functions, dendritic cell activation, and Th2 cytokine responses during the initial phases of IT in an antigen non-specific manner. While there was some inter-individual variation, in many patients, suppression appeared to be temporary.
Capsule SummaryMOIT can be effective in desensitizing children with severe IgE-mediated CMA, with most tolerating markedly increased amounts of cow's milk protein over time and demonstrating changes in serologic markers. KeywordsCow's milk; food allergy; IgE; prognosis; desensitization; tolerance; oral immunotherapy To the EditorCow's milk allergy (CMA) is a common disorder for which there is no effective treatment. Currently, the standard of care is strict food avoidance, although there have been several recent studies with encouraging results using oral and sublingual immunotherapy (OIT and SLIT) for the treatment of food allergy. [1][2][3][4][5][6][7][8] One such study evaluated the safety and efficacy of OIT for CMA in a randomized, double-blind, placebo-controlled trial, and this report summarizes the subsequent, open label phase of this study. 8 Participants who successfully completed the double-blind portion of the milk oral immunotherapy (MOIT) study were continued on measured dairy intake at home daily. The objectives of this phase were to determine, in children with severe IgE-mediated CMA: 1) the safety of continued milk intake after OIT, and 2) the efficacy in conferring tolerance to increasing amounts of cow's milk protein.Only those who could tolerate > 2,540mg in their post-MOIT challenge were eligible for this institutional review board approved protocol. Initial home doses were based on the nature and frequency of symptoms experienced during MOIT, milk protein threshold determined in the Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Fifteen subjects aged 6-16 years were included with follow-up ranging from 3 to 17months (see Table I). Initial milk doses ranged from 500 to 4,000mg (median 500). Fourteen participants were able to escalate daily doses by 2-32-fold (median 9-fold) with maximum doses ranging from 1,000 to 16,000mg (median 7,000). NIH Public AccessAfter 13 to 75weeks (median 17) of open label dosing, challenges were conducted on 13 participants, with the timing of challenges based on post-MOIT challenge outcome and success with home dosing. Six tolerated 16,000mg with no reaction and 7 reacted at 3,000 to 16,000mg.Of the 3 that reacted at 16,000mg, reactions included oral itch with abdominal pain, sneezing, and mild cough, respectively. One subject developed localized hives at 10,000mg and 2 experienced localized hives at 3,000mg. One required albuterol and diphenhydramine for cough, nausea and abdominal pain that developed at 6,000mg. Challenges were not conducted on two due to ongoing reactions with home dose escalations.End point titration...
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