Article

Sublingual immunotherapy for peanut allergy: Clinical and immunologic evidence of desensitization

Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, NC 27710, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.25). 03/2011; 127(3):640-6.e1. DOI: 10.1016/j.jaci.2010.12.1083
Source: PubMed

ABSTRACT There are no treatments currently available for peanut allergy. Sublingual immunotherapy (SLIT) is a novel approach to the treatment of peanut allergy.
We sought to investigate the safety, clinical effectiveness, and immunologic changes with SLIT in children with peanut allergy.
In this double-blind, placebo-controlled study subjects underwent 6 months of dose escalation and 6 months of maintenance dosing followed by a double-blind, placebo-controlled food challenge.
Eighteen children aged 1 to 11 years completed 12 months of dosing and the food challenge. Dosing side effects were primarily oropharyngeal and uncommonly required treatment. During the double-blind, placebo-controlled food challenge, the treatment group safely ingested 20 times more peanut protein than the placebo group (median, 1,710 vs 85 mg; P = .011). Mechanistic studies demonstrated a decrease in skin prick test wheal size (P = .020) and decreased basophil responsiveness after stimulation with 10(-2) μg/mL (P = .009) and 10(-3) μg/mL (P = .009) of peanut. Peanut-specific IgE levels increased over the initial 4 months (P = .002) and then steadily decreased over the remaining 8 months (P = .003), whereas peanut-specific IgG4 levels increased during the 12 months (P = .014). Lastly, IL-5 levels decreased after 12 months (P = .015). No statistically significant changes were found in IL-13 levels, the percentage of regulatory T cells, or IL-10 and IFN-γ production.
Peanut SLIT is able to safely induce clinical desensitization in children with peanut allergy, with evidence of immunologic changes suggesting a significant change in the allergic response. Further study is required to determine whether continued peanut SLIT is able to induce long-term immune tolerance.

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    • "However, studies have shown down-regulation of the allergen-specific Th2 response, increase of the Th1 response and induction of regulatory T cells, in association with peanut immunotherapy. In particular, successful peanut immunotherapy has resulted in a peanut-specific IgE decrease, peanut skin prick test decrease, peanut IgG and IgG4 increase, as well as decreased IL-4, IL-5 and IL-13 and increased IL-10 and TGF-b cytokine production [28,31,38,41]. Microarray data has demonstrated down-regulation of genes in several apoptosis pathways in patient T cells, although it is not clear whether these changes included apoptosis of antigen-specific cells as well as total peripheral blood T cells [28]. "
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    ABSTRACT: Peanut allergy is common and can be a cause of severe, life-threatening reactions. It is rarely outgrown like other food allergies, such as egg and milk. Peanut allergy has a significant effect on the quality of life of sufferers and their families, due to dietary and social restrictions, but mainly stemming from fear of accidental peanut ingestion. The current management consists of strict avoidance, education and provision of emergency medication, but a disease- modifying therapy is needed for peanut allergy. Recent developments involve the use of immunotherapy, which has shown promise as an active form of treatment. Various routes of administration are being investigated, including subcutaneous, oral, sublingual and epicutaneous routes. Other forms of treatment, such as the use of vaccines and anti-IgE molecules, are also under investigation. So far, results from immunotherapy studies have shown good efficacy in achieving desensitisation to peanut with a good safety profile. However, the issue of long-term tolerance has not been fully addressed yet and larger, phase III studies are required to further investigate safety and efficacy. An assessment of cost/benefit ratio is also required prior to implementing this form of treatment. The use of immunotherapy for peanut allergy is not currently recommended for routine clinical use and should not be attempted outside specialist allergy units.
    09/2014; 4(1):30. DOI:10.1186/2045-7022-4-30
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    • "This has been demonstrated in the natural development of tolerance to cow's milk (Savilahti et al., 2010; Tomicic et al., 2009; Ruiter et al., 2007) and hen's egg (Tomicic et al., 2009; Lemon-Mule et al., 2008) as well as in desensitisation by allergen-specific immunotherapy to peanut (Vickery et al., 2013; Kim et al., 2011; Jones et al., 2009), cow's milk (Skripak et al., 2008), hen's egg (Burks et al., 2012), hazelnut (Enrique et al., 2005), peach (Fernandez-Rivas et al., 2009) and kiwi (Mempel et al., 2003; Kerzl et al., 2007). Although the increase in specific IgG4 level has commonly been reported to be associated with a decrease in the specific IgE level (Vickery et al., 2013; Savilahti et al., 2010; Jones et al., 2009; Kerzl et al., 2007; Ruiter et al., 2007), in many cases no such decrease was observed (Kim et al., 2011; Enrique et al., 2005; Skripak et al., 2008; Lemon-Mule et al., 2008; Mempel et al., 2003; Fernandez-Rivas et al., 2009). This has led to the premise that analysis of specific IgE reactivity as well as specific IgG4 reactivity may be informative when studying the mechanisms involved in tolerance induction. "
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    ABSTRACT: Development and maintenance of tolerance to food allergens appears to be associated with alterations in antigen specific IgE and IgG4 responses. Previous studies have focused only on comparing IgE and IgG4 linear epitope recognition patterns but take no account of conformational epitopes. The aim of this study was to compare Ara h 1-specific IgE and IgG4 epitope recognition patterns in patients with severe peanut allergy, applying a method allowing for identification of both linear and conformational epitopes. Polyclonal sera from three individual patients, suffering from severe allergic reaction to peanuts, including anaphylaxis, were used to analyse the IgE and IgG4 epitope recognition patterns of the major peanut allergen Ara h 1. Epitope identification was conducted by competitive immuno-screening of a phage-displayed random heptamer peptide library. Resulting epitope-mimicking sequences were aligned for identification of consensus sequences and localised on the surface of the Ara h 1 molecule by a computer-based algorithm. All epitope-mimicking sequences identified were found to correspond to conformational epitopes. Each individual patient had his/her own distinct IgE as well as IgG4 epitope recognition profile, though some important IgE epitopes were common to all patients. In general the IgG4 epitope pattern was more heterogeneous than the IgE pattern, did not coincide with IgE epitopes and had a lower affinity than IgE. This study demonstrated the usefulness of the phage-display technology in distinguishing between the epitope pattern of IgE and IgG4, giving detailed information on fine specificity and affinity. Competitive immuno-screening of phage-display random peptide libraries could be a future valuable tool to study the balance and dynamics of the IgE and IgG4 epitope recognition repertoire and provide a diagnostic tool giving information on the associated allergic phenotype.
    Molecular Immunology 12/2013; 58(2):169-176. DOI:10.1016/j.molimm.2013.11.014 · 3.00 Impact Factor
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    • "In this approach, the food is administered sublingually, held in the mouth for few minutes, and then spit or swallowed. Several studies, with hazelnut, milk, peanut, and peach have demonstrated the benefit of SLIT in increasing the amount of the food tolerated on double-blind placebo-controlled food challenge (DBPCFC).27-30 Side effects are generally mild, primarily limited to oropharyngeal symptoms, and rarely requiring oral antihistamine administration. "
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    ABSTRACT: Food allergy has increased dramatically in prevalence over the past decade in westernized countries, and is now a major public health problem. Unfortunately for patients with food allergy, there is no effective therapy beyond food allergen avoidance, and rapid medical treatment for accidental exposures. Recently, oral immunotherapy (OIT) has been investigated as a treatment for this problem. In this review, we will discuss the progress in developing OIT for food allergy, including a novel approach utilizing Xolair (anti-IgE monoclonal antibody, omalizumab) in combination with OIT. This combination may enhance both the safety and efficacy of oral immunotherapy, and could lead to a widely available and safe therapy for food allergy.
    Allergy, asthma & immunology research 01/2013; 5(1):3-15. DOI:10.4168/aair.2013.5.1.3 · 3.08 Impact Factor
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