The degree of whey hydrolysis does not uniformly affect <i>in vitro</i> basophil and <scp>T</scp> cell responses of cow's milk‐allergic patients

Meulenbroek, Laura A.P.M.; Oliveira, Sabrina; Jäger, Cornelie; Klemans, Rob J.B.; Lebens, Ans F.M.; Baalen, T. van; Knulst, André C.; Bruijnzeel-Koomen, Carla A.F.M.; Garssen, Johan; Knippels, L.M.J.; Hoffen, Els van

doi:10.1111/cea.12254

Cited by 23 publications

(18 citation statements)

References 47 publications

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“…A decreased allergenicity, confirmed by protein degradation, inhibition of mast cell degranulation, reduction of ear swelling, and reduction of T‐cell proliferation was also observed in whey protein concentrates after hydrolysis with a time‐dependent effect (Knipping and others ). Meulenbroek and others () stated that in some patients this time effect is not evident, indicating that the degree of hydrolysis is not decisive, but the presence and stability of IgE and T‐cell epitopes in the hydrolysates are recognized by individual patients. As stated previously, heat treatment seems to increase the effect of enzymatic hydrolysis due to the possible exposure of cleavage sites as a result of thermal denaturation and, subsequently, enhancing the susceptibility of protein to undergo proteolysis.…”

Section: Effect Of Processing Food Matrix and Digestibility On Milkmentioning

confidence: 99%

Bovine Milk Allergens: A Comprehensive Review

Villa

Costa

Oliveira

et al. 2017

Comp Rev Food Sci Food Safe

190

145

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Cow milk allergy is one of the most common food allergies in early childhood and often persists through adult life, forcing an individual to a complete elimination diet. Milk proteins are present in uncounted food products, such as cheese, yogurt, or bakery item, exposing allergic persons to a constant threat. Many efforts have been made to overcome this global problem and to improve the life quality of allergic individuals. First, proper and reliable food labeling is fundamental for consumers, but the verification of its compliance is also needed, which should rely on accurate and sensitive analytical methods to detect milk allergens in processed foods. At the same time, strategies to reduce milk allergenicity, such as immunotherapy or the use of food processing techniques to modify allergen structure, have to be extensively studied. Recent research findings on the applicability of food processing, such as heat treatment, fermentation, or high pressure, have revealed great potential in reducing milk allergenicity. In this review, significant research advances on cow milk allergy are explored, focusing on prevalence, diagnosis, and therapy. Molecular characterization of cow milk allergens and cross-reactivity with other nonbovine milk species are described, as well as the effects of processing, food matrix, and digestibility on milk allergenicity. Additionally, analytical methods for the detection of milk allergens in food are described, from immunoassays and mass spectrometry methods for protein analysis to real-time polymerase chain reaction for DNA analysis.

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Section: Effect Of Processing Food Matrix and Digestibility On Milkmentioning

confidence: 99%

Bovine Milk Allergens: A Comprehensive Review

Villa

Costa

Oliveira

et al. 2017

Comp Rev Food Sci Food Safe

190

145

View full text Add to dashboard Cite

show abstract

“…However, the evidence is not strong [11]. It is unclear which biochemical and biophysical properties are important for a tolerogenic effect of a hypoallergenic IF, although it has been suggested that the degree of hydrolysis (DH) is not the only contributing factor [12]. Furthermore, oral immunotherapy is emerging as a viable option for the treatment of food allergy [13, 14].…”

Section: Introductionmentioning

confidence: 99%

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow’s Milk Allergy

Jensen

Larsen

Madsen

et al. 2019

Int Arch Allergy Immunol

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Background: Infant formulas (IFs) based on hydrolysed cow’s milk proteins are central in the management of cow’s milk allergy (CMA) in infants and small children. New IF compositions with improved prevention and treatment properties are needed, along with appropriate preclinical animal models, to evaluate these properties before introduction into humans. Objectives: We aimed to develop preclinical models for the assessment of the primary preventive and desensitising capacity of cow’s milk IF in allergy-prone, high-IgE responder Brown Norway rats. Method: Preventive capacity was assessed in cow’s milk-naïve rats given a 2- or 4-week regimen of whey-based extensively hydrolysed IF (eHF), partially hydrolysed IF (pHF), or intact β-lactoglobulin (BLG) ad libitum in drinking bottles, followed by intraperitoneal (i.p.) immunisation with BLG. Desensitising capacity was assessed in orally BLG-sensitised rats after a 3- or 6-week regimen of eHF, pHF, or intact BLG administration in drinking bottles, followed by i.p. challenge with BLG. Primary preventive and desensitising capacity were analysed by serum BLG-specific IgG1 and IgE. Results: The preventive regimens did not induce detectable BLG-specific IgG1 or IgE in cow’s milk-naïve rats. A preventive regimen consisting of pHF or BLG, but not eHF, induced complete tolerance to BLG, as demonstrated by the absence of BLG-specific IgE following i.p. immunisation. Desensitising regimens had a limited effect on BLG-specific IgG1 or IgE when comparing sensitised rats before and after treatment. Challenge with BLG (i.p.) increased BLG-specific IgE in all treatment regimens except for in the BLG group, suggesting a limited desensitising capacity of IF based on hydrolysates and a need for the presence of intact allergen for desensitisation. Conclusions: The presented models highlight that different mechanisms are at play in the induction of de novo tolerance to cow’s milk proteins and the desensitisation of CMA. Different IF products may be needed for the primary prevention and treatment of CMA.

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“…In general, clinical studies emphasize that eHFs should be the first choice for prevention of symptoms, as eHFs have been estimated to cause allergic reaction in approximately 5–10% of infants with CMA, while pHFs have been estimated to cause allergic reaction in between 33% and 50% of cow's milk allergic infants . However, the degree of hydrolysis does not uniformly affect the allergenic potency in different cow's milk allergic patients . Further the residual allergenicity may in addition be influenced by the protein source .…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Immunogenicity and Allergenicity of Two Cow's Milk Hydrolysates – A Study in Brown Norway Rats

2015

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Hypoallergenic infant formulas based on hydrolysed milk proteins are used in the diet for cow's milk allergic infants. For a preclinical evaluation of the immunogenicity and allergenicity of new protein ingredients for such hypoallergenic infant formulas as well as for the investigation of which characteristics of hydrolysates that contribute to allergenicity, in vivo models are valuable tools. In this study, we examine the immunogenicity and allergenicity of two hydrolysates in a Brown Norway (BN) rat model, using i.p. dosing, which allows for the use of small quantities. Intact BLG, hydrolysed BLG and a hydrolysed whey product suitable for use in extensively hydrolysed formulas were thoroughly characterized for protein chemical features and administered to BN rats by i.p. immunization with or without adjuvant. Sera were analysed for specific IgG and IgE for evaluation of sensitizing capacity, immunogenicity and antibody-binding capacity. For evaluation of eliciting capacity a skin test was performed. The study showed that the hydrolysates had no residual allergenicity, lacking the capacity to sensitize and elicit reactions in the BN rats. Dosing with or without adjuvant induced a large difference in immunogenicity. Only antibodies from rats sensitized to intact BLG with adjuvant were able to bind the hydrolysates, and the whey-based hydrolysate only showed immunogenicity when dosed with adjuvant. This study showed that hydrolysates can be evaluated by an i.p. animal model, but that the choice of in vitro tests used for evaluation of antibody responses may greatly influence the result as well as may the use of adjuvant.

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The degree of whey hydrolysis does not uniformly affect in vitro basophil and T cell responses of cow's milk‐allergic patients

Cited by 23 publications

References 47 publications

Bovine Milk Allergens: A Comprehensive Review

Bovine Milk Allergens: A Comprehensive Review

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow’s Milk Allergy

Characterization of the Immunogenicity and Allergenicity of Two Cow's Milk Hydrolysates – A Study in Brown Norway Rats

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