Tolerance To Extensively heated Milk In Children With Cow’s Milk Allergy

Department of Pediatrics and Jaffe Food Allergy Institute, Mount Sinai School of Medicine, New York, NY 10029, USA.
The Journal of allergy and clinical immunology (Impact Factor: 11.48). 08/2008; 122(2):342-7, 347.e1-2. DOI: 10.1016/j.jaci.2008.05.043
Source: PubMed


Cow's milk allergy is the most common childhood food allergy. Previously we noted that children who outgrew their milk allergy had milk-specific IgE antibodies primarily directed against conformational epitopes; those with persistent milk allergy also had IgE antibodies directed against specific sequential epitopes.
Because high temperature largely destroys conformational epitopes, we hypothesized that some children with milk allergy would tolerate extensively heated (baked) milk products.
Children with milk allergy were challenged with heated milk products; heated milk-tolerant subjects were subsequently challenged with unheated milk. Heated milk-tolerant, unheated milk-reactive subjects ingested heated milk products for 3 months and were then re-evaluated. Immune responses were assessed in all subjects; growth and intestinal permeability were followed in heated milk-tolerant subjects.
One hundred children (mean age, 7.5 years; range, 2.1-17.3 years) underwent heated milk challenges. Sixty-eight subjects tolerated extensively heated milk only, 23 reacted to heated milk, and 9 tolerated both heated and unheated milk. Heated milk-reactive subjects had significantly larger skin prick test wheals and higher milk-specific and casein-specific IgE levels than other groups. At 3 months, subjects ingesting heated milk products had significantly smaller skin prick test wheals and higher casein-IgG(4) compared with baseline; other immunologic parameters, growth, and intestinal permeability were not significantly different. Heated milk-reactive subjects had more severe symptoms during heated milk challenge than heated milk-tolerant subjects experienced during their unheated milk challenge.
The majority (75%) of children with milk allergy tolerate heated milk.

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    • "Clinical trials have demonstrated that a high percentage of children, with milk and egg allergies, tolerated heated products with milk or egg. This clinical effect goes along with increased levels of specific IgG4 antibodies (Lemon-Mulé et al., 2008; Nowak-Wegrzyn et al., 2008). We have previously demonstrated that food processing, such as treatments based on pressure and heat, seem to influence the IgE binding capacity of nut proteins (Cabanillas et al., 2012). "
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    ABSTRACT: This study aimed to analyze the influence of thermal processing on the IgE binding properties of three forms of peanut, its effects in the content of individual allergens and IgE cross-linking capacity in effector cells of allergy. Three forms of peanut were selected and subjected to thermal processing. Immunoreactivity was evaluated by means of immunoblot or ELISA inhibition assay. Specific antibodies were used to identify changes in the content of the main allergens in peanut samples. The ability of treated peanut to cross-link IgE was evaluated in a basophil activation assay and Skin Prick Testing (SPT). The results showed that thermal/pressure treatments at specific conditions had the capacity to decrease IgE binding properties of protein extracts from peanut. This effect went along with an altered capacity to activate basophils sensitized with IgE from patients with peanut allergy and the wheal size in SPT. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · Sep 2015 · Food Chemistry
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    • "The use of processed food with diminished IgE binding capacity is also an attractive strategy for oral immunotherapy. Clinical trials have shown that around 70% of tested children, with milk and egg allergies, tolerated heated products with milk or egg with an association of increased levels of specific IgG4 antibodies and decreased in SPT wheals size (Lemon-Mulé et al., 2008; Nowak-Wegrzyn et al., 2008). "
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    ABSTRACT: The aim of this study was to investigate changes in walnut allergenicity after processing treatments by in vitro techniques and physiologically relevant assays. The allergenicity of walnuts subjected to high hydrostatic pressure and thermal/pressure treatments was evaluated by IgE-immunoblot and antibodies against walnut major allergen Jug r 4. The ability of processed walnut to cross-link IgE on effector cells was evaluated using a rat basophil leukaemia cell line and by skin prick testing. Susceptibility to gastric and duodenal digestion was also evaluated. The results showed that walnuts subjected to pressure treatment at 256 kPa, 138 °C, were able to diminish the IgE cross-linking capacity on effector cells more efficiently than high pressure treated walnuts. IgE immunoblot confirmed these results. Moreover, higher susceptibility to digestion of pressure treated walnut proteins was observed. The use of processed walnuts with decreased IgE binding capacity could be a potential strategy for walnut tolerance induction.
    Full-text · Article · Aug 2014 · Food Chemistry
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    • "Children outgrowing their milk allergy have IgE primarily directed at conformational epitopes, whereas children with persistent milk allergy show higher levels of IgE directed to sequential epitopes.16,8 Those children reacting to heated milk have initially higher casein and beta-lactoglobulin IgE levels and are at higher risk for systemic reactions.17 "
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    ABSTRACT: The aim of study was to assess the value of recombinants in predicting the degree of symptoms in children with and without anaphylaxis to cow's milk. The study included 79 children (70±40 months) referred to the Allergological Unit of the Pediatric Department between the years 2008-2012. Group A was composed of 17 children (78±49.6 months) with anaphylaxis after ingestion of milk. Group B was composed of 62 children (73.1±38.6 months) without a history of anaphylaxis, but with less severe symptoms (gastrointestinal and/or skin symptoms). All patients from Group B had a positive open challenge with cow's milk. All patients underwent an allergic evaluation and blood samples were collected to test for IgE to recombinans of milk (nBos d 4, 5, 8). A significant difference in nBos d 8 emerged with higher levels in Group A (median [IQR]=2.80 [0.91-16.1]) than B (0.65 [0.24-1.67]; P=0.006), whereas there were no statistically significant differences for nBos d 4 and 5. The recombinants' sum was higher in Group A than B: 8.39 [2.72-41.39] vs 3.04 [1.85-7.31] kUA/L; P=0.044. The recombinant nBos d 8 was superior to the other recombinants in identifying children at risk for anaphylaxis, with an area under the curve of 0.718 (95% CI, 0.57-0.86, P=0.006). Considering a cutoff of 1.8 kUA/L, nBos d 8 had the most favorable sensitivity and specificity ratio (sensitivity=0.65, specificity=0.77) with an odd ratio of 6.02 (95% C.I: 1.89-19.23). This study suggested 2 phenotypes of allergic children, "high-anaphylaxis-risk" and "milder-risk". These types can be differentiated through measuring the level of IgE to nBos d 8.
    Full-text · Article · Mar 2014 · Allergy, asthma & immunology research
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