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Reducing Allergenicity by Proteolysis

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Agents of Change

Part of the book series: Food Engineering Series ((FSES))

Abstract

Cow’s milk allergy is a health problem of growing concern. However, it is possible to modify the inherent allergenic properties of milk proteins by proteolysis typically for use in hypoallergenic infant formulas (HA IFs). HA IFs are widely used in the management cow’s milk allergy (CMA) and may be applicable in the prevention and treatment of CMA. Here we provide an overview of milk protein allergens and the factors involved in the in vivo digestibility of these, including intestinal tract proteases, pH, surfactant, matrix, processing, and glycation. The industrial-scale production of HA IF involves the use of common commercially available proteases followed by drying and additions of other dietary nutrients. To some extent, the degree of hydrolysis determines the overall allergenicity of the HA IF, which is influenced by parameters such as the specific proteases used, hydrolysis duration, enzyme to protein ratio, matrix, and processing. Several molecular assays can be used to determine the degree of hydrolysis and evaluate product allergenicity in vitro, however animal models may represent an important tool for evaluation of sensitising and primary preventing capacities of HA IFs.

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References

  • Aalberse RC (2000) Structural biology of allergens. J Allergy Clin Immunol 106:228–238

    Google Scholar 

  • Adams JJ, Anderson BF, Norris GE et al (2006) Structure of bovine beta-lactoglobulin (variant A) at very low ionic strength. J Struct Biol 154:246–254

    Google Scholar 

  • Arnon R, Van Regenmortel MH (1992) Structural basis of antigenic specificity and design of new vaccines. FASEB J 6:3265–3274

    Google Scholar 

  • Asgeirsson B, Bjarnason JB (1991) Structural and kinetic properties of chymotrypsin from Atlantic cod (Gadus morhua). Comparison with bovine chymotrypsin. Comp Biochem Physiol B 99:327–335

    Google Scholar 

  • Astwood JD, Leach JN, Fuchs RL (1996) Stability of food allergens to digestion in vitro. Nat Biotechnol 14:1269–1273

    Google Scholar 

  • Bahna SL (2008) Hypoallergenic formulas: optimal choices for treatment versus prevention. Ann Allergy Asthma Immunol 101:453–459

    Google Scholar 

  • Bannon GA (2004) What makes a food protein an allergen? Curr Allergy Asthma Rep 4:43–46

    Google Scholar 

  • Barlow DJ, Edwards MS, Thornton JM (1986) Continuous and discontinuous protein antigenic determinants. Nature 322:747–748

    Google Scholar 

  • Benedé S, López-Expósito I, Giménez G et al (2014) Mapping of IgE epitopes in in vitro gastroduodenal digests of β-lactoglobulin produced with human and simulated fluids. Food Res Int 62:1127–1133

    Google Scholar 

  • Benedé S, López-Fandiño R, Molina E (2017) Assessment of IgE reactivity of β-Casein by Western blotting after digestion with simulated gastric fluid. In: Methods in molecular biology. Humana Press, Clifton, pp 165–175

    Google Scholar 

  • Bindels JG, Boerma JA (1994) Hydrolysed cow’s milk formulae. Pediatr Allergy Immunol 5:189–190

    Google Scholar 

  • Biscola V, Tulini FL, Choiset Y et al (2016) Proteolytic activity of Enterococcus faecalis VB63F for reduction of allergenicity of bovine milk proteins. J Dairy Sci 99:5144–5154

    Google Scholar 

  • Bleumink E, Young E (1968) Identification of the atopic allergen in cow’s milk. Int Arch Allergy Appl Immunol 34:521–543

    Google Scholar 

  • Bøgh KL, Madsen CB (2016) Food allergens: is there a correlation between stability to digestion and allergenicity? Crit Rev Food Sci Nutr 56:1545–1567

    Google Scholar 

  • Bøgh KL, Barkholt V, Madsen CB (2013) The sensitising capacity of intact β-lactoglobulin is reduced by co-administration with digested β-lactoglobulin. Int Arch Allergy Immunol 161:21–36

    Google Scholar 

  • Bøgh KL, Barkholt V, Madsen CB (2015) Characterization of the immunogenicity and allergenicity of two cow’s milk hydrolysates - a study in brown Norway rats. Scand J Immunol 81:274–283

    Google Scholar 

  • Broekman HCH, Eiwegger T, Upton J, Bøgh KL (2015) IgE – the main player of food allergy. Drug Discov Today Dis Model 17–18:37–44

    Google Scholar 

  • CAC (2003) Codex Alimentarius Commission - Alinorm 03/34: Joint FAO/WHO Food Standard Programme, Codex Alimentarius Commission, Twenty-Fifth Session, Rome, Italy 30 June - 5 July, 2003

    Google Scholar 

  • Cawthern KM, Permyakov E, Berliner LJ (1996) Membrane-bound states of α-lactalbumin: implications for the protein stability and conformation. Protein Sci 5:1394–1405

    Google Scholar 

  • Chapman MD (2008) Allergen nomenclature. Clin Allergy Immunol 21:47–58

    Google Scholar 

  • Chatchatee P, Järvinen KM, Bardina L et al (2001) Identification of IgE and IgG binding epitopes on beta- and kappa-casein in cow’s milk allergic patients. Clin Exp Allergy 31:1256–1262

    Google Scholar 

  • Corzo-Martínez M, Soria AC, Belloque J et al (2010) Effect of glycation on the gastrointestinal digestibility and immunoreactivity of bovine β-lactoglobulin. Int Dairy J 20:742–752

    Google Scholar 

  • Crittenden RG, Bennett LE (2005) Cow’s milk allergy: a complex disorder. J Am Coll Nutr 24:582S–591S

    Google Scholar 

  • Dosa S, Pesce AJ, Ford DJ et al (1979) Immunological properties of peptic fragments of bovine serum albumin. Immunology 38:509–517

    Google Scholar 

  • Duan C, Yang L, Li A et al (2014) Effects of enzymatic hydrolysis on the allergenicity of whey protein concentrates. Iran J Allergy Asthma Immunol 13:231–239

    Google Scholar 

  • Dupont D, Mackie AR (2015) Static and dynamic in vitro digestion models to study protein stability in the gastrointestinal tract. Drug Discov Today Dis Model 17–18:23–27

    Google Scholar 

  • Dupont D, Mandalari G, Molle D et al (2010) Comparative resistance of food proteins to adult and infant in vitro digestion models. Mol Nutr Food Res 54:767–780

    Google Scholar 

  • EFSA (2010) Scientific Opinion on the assessment of allergenicity of GM plants and microorganisms and derived food and feed. EFSA J 8:1700

    Google Scholar 

  • Eigenmann P, Madrazo-de la Garza JA, Nutten S, O’Mahony L (2018) Towards optimised management of cow’s milk protein allergy - European medical journal. EMJ Allergy Immunol 3:50–59

    Google Scholar 

  • El Mecherfi K-E, Rouaud O, Curet S et al (2015) Peptic hydrolysis of bovine beta-lactoglobulin under microwave treatment reduces its allergenicity in an ex vivo murine allergy model. Int J Food Sci Technol 50:356–364

    Google Scholar 

  • Erickson RH, Kim YS (1990) Digestion and absorption of dietary protein. Annu Rev Med 41:133–139

    Google Scholar 

  • Etherington DJ, Taylor WH (1970) The pepsins from human gastric mucosal extracts. Biochem J 118:587–594

    Google Scholar 

  • FAO/WHO (2001) Evaluation of Allergenicity of Genetically Modified Foods. Report of a Joint FAO/WHO Expert Consulation on Allergenicity of Food Derived from Biotechnology, 22-25 january 2001. Food and Agriculture organisation of the United Nations (FAO), Rome

    Google Scholar 

  • Farkas V, Vass E, Hanssens I et al (2005) Cyclic peptide models of the Ca2+-binding loop of alpha-lactalbumin. Bioorg Med Chem 13:5310–5320

    Google Scholar 

  • Ferguson TA, Peters T, Reed R et al (1983) Immunoregulatory properties of antigenic fragments from bovine serum albumin. Cell Immunol 78:1–12

    Google Scholar 

  • Fiocchi A, Schünemann HJ, Brozek J et al (2010) Diagnosis and Rationale for Action Against Cow’s Milk Allergy (DRACMA): a summary report. J Allergy Clin Immunol 126:1119–1128

    Google Scholar 

  • Fiocchi A, Schunemann H, Ansotegui I et al (2018) The global impact of the DRACMA guidelines cow’s milk allergy clinical practice. World Allergy Organ J 11:2

    Google Scholar 

  • Fritsché R (2009) Utility of animal models for evaluating hypoallergenicity. Mol Nutr Food Res 53:979–983

    Google Scholar 

  • Fritsché R, Bonzon M (1990) Determination of cow milk formula allergenicity in the rat model by in vitro mast cell triggering and in vivo IgE induction. Int Arch Allergy Appl Immunol 93:289–293

    Google Scholar 

  • Fritsché R, Pahud JJ, Pecquet S, Pfeifer A (1997) Induction of systemic immunologic tolerance to beta-lactoglobulin by oral administration of a whey protein hydrolysate. J Allergy Clin Immunol 100:266–273

    Google Scholar 

  • Fu T-J, Abbott UR, Hatzos C (2002) Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid-a comparative study. J Agric Food Chem 50:7154–7160

    Google Scholar 

  • Gass J, Vora H, Hofmann AF et al (2007) Enhancement of dietary protein digestion by conjugated bile acids. Gastroenterology 133:16–23

    Google Scholar 

  • Golkar A, Milani JM, Vasiljevic T (2019) Altering allergenicity of cow’s milk by food processing for applications in infant formula. Crit Rev Food Sci Nutr 59:159–172

    Google Scholar 

  • Guo M, Ahmad S (2014) Formulation guidelines for infant formula. In: Human milk biochemistry and infant formula manufacturing technology. Woodhead Publishing, Cambridge, pp 141–171

    Google Scholar 

  • Haddad ZH, Kalra V, Verma S (1979) IgE antibodies to peptic and peptic-tryptic digests of betalactoglobulin: significance in food hypersensitivity. Ann Allergy 42:368–371

    Google Scholar 

  • Hemmings O, Kwok M, McKendry R, Santos AF (2018) Basophil activation test: old and new applications in allergy. Curr Allergy Asthma Rep 18:77

    Google Scholar 

  • Herman RA, Woolhiser MM, Ladics GS et al (2007) Stability of a set of allergens and non-allergens in simulated gastric fluid. Int J Food Sci Nutr 58:125–141

    Google Scholar 

  • Hochwallner H, Schulmeister U, Swoboda I et al (2014) Cow’s milk allergy: from allergens to new forms of diagnosis, therapy and prevention. Methods 66:22–33

    Google Scholar 

  • Høst A, Koletzko B, Dreborg S et al (1999) Dietary products used in infants for treatment and prevention of food allergy. Joint Statement of the European Society for Paediatric Allergology and Clinical Immunology (ESPACI) Committee on Hypoallergenic Formulas and the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee on Nutrition. Arch Dis Child 81:80–84

    Google Scholar 

  • Huby RD, Dearman RJ, Kimber I (2000) Why are some proteins allergens? Toxicol Sci 55:235–246

    Google Scholar 

  • Inouye K, Fruton JS (1967) Studies on the specificity of pepsin. Biochemistry 6:1765–1777

    Google Scholar 

  • IUIS (2019) IUIS allergen nomenclature (http://www.allergen.org)

  • Iwamoto H, Matsubara T, Nakazato Y et al (2016) Evaluation of the antigenicity of hydrolyzed cow’s milk protein formulas using the mouse basophil activation test. Toxicol Lett 242:53–59

    Google Scholar 

  • James AH, Baron JH (1962) Discussion on the physiological and clinical assessment of gastric function. Proc R Soc Med 55:71–75

    Google Scholar 

  • Järvinen KM, Chatchatee P, Bardina L et al (2001) IgE and IgG binding epitopes on alpha-lactalbumin and beta-lactoglobulin in cow’s milk allergy. Int Arch Allergy Immunol 126:111–118

    Google Scholar 

  • Järvinen K-M, Beyer K, Vila L et al (2002) B-cell epitopes as a screening instrument for persistent cow’s milk allergy. J Allergy Clin Immunol 110:293–297

    Google Scholar 

  • Jensen LH, Larsen JM, Madsen CB et al (2019) Preclinical brown Norway rat models for the assessment of infant formulas in the prevention and treatment of cow’s milk allergy. Int Arch Allergy Immunol 178:307–314

    Google Scholar 

  • Jost R, Meister N, Monti JC (1991) Preparation of a hypoallergenic whey protein hydrolyzate and food. US Patent US5039532A

    Google Scholar 

  • Kattan JD, Cocco RR, Järvinen KM (2011) Milk and soy allergy. Pediatr Clin North Am 58:407–426

    Google Scholar 

  • Kontopidis G, Holt C, Sawyer L (2004) Invited review: β-Lactoglobulin: binding properties, structure, and function. J Dairy Sci 87:785–796

    Google Scholar 

  • Li Z, Luo Y, Feng L, Liao P (2013) Effect of Maillard reaction conditions on antigenicity of β-lactoglobulin and the properties of glycated whey protein during simulated gastric digestion. Food Agric Immunol 24:433–443

    Google Scholar 

  • Liu X, Luo Y, Li Z (2012) Effects of pH, temperature, enzyme-to-substrate ratio and reaction time on the antigenicity of casein hydrolysates prepared by papain. Food Agric Immunol 23:69–82

    Google Scholar 

  • Lucas JSA, Cochrane SA, Warner JO, Hourihane JOB (2008) The effect of digestion and pH on the allergenicity of kiwifruit proteins. Pediatr Allergy Immunol 19:392–398

    Google Scholar 

  • Macierzanka A, Sancho AI, Mills ENC et al (2009) Emulsification alters simulated gastrointestinal proteolysis of β-casein and β-lactoglobulin. Soft Matter 5:538–550

    Google Scholar 

  • Mandalari G, Adel-Patient K, Barkholt V et al (2009a) In vitro digestibility of beta-casein and beta-lactoglobulin under simulated human gastric and duodenal conditions: a multi-laboratory evaluation. Regul Toxicol Pharmacol 55:372–381

    Google Scholar 

  • Mandalari G, Mackie AM, Rigby NM et al (2009b) Physiological phosphatidylcholine protects bovine beta-lactoglobulin from simulated gastrointestinal proteolysis. Mol Nutr Food Res 53(Suppl 1):S131–S139

    Google Scholar 

  • Marchesseau S, Mani J-C, Martineau P et al (2002) Casein interactions studied by the surface plasmon resonance technique. J Dairy Sci 85:2711–2721

    Google Scholar 

  • Marciani L, Gowland PA, Spiller RC et al (2001) Effect of meal viscosity and nutrients on satiety, intragastric dilution, and emptying assessed by MRI. Am J Physiol Gastrointest Liver Physiol 280:G1227–G1233

    Google Scholar 

  • Martinez MJ, Martos G, Molina E, Pilosof AMR (2016) Reduced β-lactoglobulin IgE binding upon in vitro digestion as a result of the interaction of the protein with casein glycomacropeptide. Food Chem 192:943–949

    Google Scholar 

  • McLaren AD, Estermann EF (1957) Influence of pH on the activity of chymotrypsin at a solid-liquid interface. Arch Biochem Biophys 68:157–160

    Google Scholar 

  • Meulenbroek LAPM, Oliveira S, den Hartog Jager CF et al (2014) The degree of whey hydrolysis does not uniformly affect in vitro basophil and T cell responses of cow’s milk-allergic patients. Clin Exp Allergy 44:529–539

    Google Scholar 

  • Michael JG (1989) The role of digestive enzymes in orally induced immune tolerance. Immunol Invest 18:1049–1054

    Google Scholar 

  • Mills ENC, Jenkins JA, Alcocer MJC, Shewry PR (2004) Structural, biological, and evolutionary relationships of plant food allergens sensitizing via the gastrointestinal tract. Crit Rev Food Sci Nutr 44:379–407

    Google Scholar 

  • Misra A, Prasad R, Das M, Dwivedi PD (2009) Probing novel allergenic proteins of commonly consumed legumes. Immunopharmacol Immunotoxicol 31:186–194

    Google Scholar 

  • Moreno FJ, Mackie AR, Mills ENC (2005a) Phospholipid interactions protect the milk allergen alpha-lactalbumin from proteolysis during in vitro digestion. J Agric Food Chem 53:9810–9816

    Google Scholar 

  • Moreno FJ, Mellon FA, Wickham MSJ et al (2005b) Stability of the major allergen Brazil nut 2S albumin (Ber e 1) to physiologically relevant in vitro gastrointestinal digestion. FEBS J 272:341–352

    Google Scholar 

  • Morisawa Y, Kitamura A, Ujihara T et al (2009) Effect of heat treatment and enzymatic digestion on the B cell epitopes of cow’s milk proteins. Clin Exp Allergy 39:918–925

    Google Scholar 

  • Mouécoucou J, Sanchez C, Villaume C et al (2003) Effects of different levels of gum arabic, low methylated pectin and xylan on in vitro digestibility of beta-lactoglobulin. J Dairy Sci 86:3857–3865

    Google Scholar 

  • Mouécoucou J, Villaume C, Sanchez C, Méjean L (2004) Beta-lactoglobulin/polysaccharide interactions during in vitro gastric and pancreatic hydrolysis assessed in dialysis bags of different molecular weight cut-offs. Biochim Biophys Acta 1670:105–112

    Google Scholar 

  • Murtagh GJ, Dumoulin M, Archer DB, Alcocer MJ (2002) Stability of recombinant 2 S albumin allergens in vitro. Biochem Soc Trans 30:913–915

    Google Scholar 

  • Murtagh GJ, Archer DB, Dumoulin M et al (2003) In vitro stability and immunoreactivity of the native and recombinant plant food 2S albumins Ber e 1 and SFA-8. Clin Exp Allergy 33:1147–1152

    Google Scholar 

  • Nacer A, Sanchez C, Villaume C et al (2004) Interactions between beta-lactoglobulin and pectins during in vitro gastric hydrolysis. J Agric Food Chem 52:355–360

    Google Scholar 

  • Niggemann B, Nies H, Renz H et al (2001) Sensitizing capacity and residual allergenicity of hydrolyzed cow’s milk formulae: results from a murine model. Int Arch Allergy Immunol 125:316–321

    Google Scholar 

  • Ofori-Anti AO, Ariyarathna H, Chen L et al (2008) Establishing objective detection limits for the pepsin digestion assay used in the assessment of genetically modified foods. Regul Toxicol Pharmacol 52:94–103

    Google Scholar 

  • Olsen JV, Ong S-E, Mann M (2004) Trypsin cleaves exclusively C-terminal to arginine and lysine residues. Mol Cell Proteomics 3:608–614

    Google Scholar 

  • Pantoja-Uceda D, Palomares O, Bruix M et al (2004) Solution structure and stability against digestion of rproBnIb, a recombinant 2S albumin from rapeseed: relationship to its allergenic properties. Biochemistry 43:16036–16045

    Google Scholar 

  • Parekh H, Bahna SL (2016) Infant formulas for food allergy treatment and prevention. Pediatr Ann 45:e150–e156

    Google Scholar 

  • Peñas E, Préstamo G, Luisa Baeza M et al (2006) Effects of combined high pressure and enzymatic treatments on the hydrolysis and immunoreactivity of dairy whey proteins. Int Dairy J 16:831–839

    Google Scholar 

  • Peram MR, Loveday SM, Ye A, Singh H (2013) In vitro gastric digestion of heat-induced aggregates of β-lactoglobulin. J Dairy Sci 96:63–74

    Google Scholar 

  • Permyakov EA, Berliner LJ (2000) Alpha-Lactalbumin: structure and function. FEBS Lett 473:269–274

    Google Scholar 

  • Polovic N, Blanusa M, Gavrovic-Jankulovic M et al (2007) A matrix effect in pectin-rich fruits hampers digestion of allergen by pepsin in vivo and in vitro. Clin Exp Allergy 37:764–771

    Google Scholar 

  • Prescott SL, Pawankar R, Allen KJ et al (2013) A global survey of changing patterns of food allergy burden in children. World Allergy Organ J 6:21

    Google Scholar 

  • Ragno V, Giampietro PG, Bruno G, Businco L (1993) Allergenicity of milk protein hydrolysate formulae in children with cow’s milk allergy. Eur J Pediatr 152:760–762

    Google Scholar 

  • Roggen EL (2006) Recent developments with B-cell epitope identification for predictive studies. J Immunotoxicol 3:137–149

    Google Scholar 

  • Rosendal A, Barkholt V (2000) Detection of potentially allergenic material in 12 hydrolyzed milk formulas. J Dairy Sci 83:2200–2210

    Google Scholar 

  • Sampson HA (2004) Update on food allergy. J Allergy Clin Immunol 113:805–819

    Google Scholar 

  • Sanchón J, Fernández-Tomé S, Miralles B et al (2018) Protein degradation and peptide release from milk proteins in human jejunum. Comparison with in vitro gastrointestinal simulation. Food Chem 239:486–494

    Google Scholar 

  • Sandberg AS, Andersson H, Hallgren B et al (1981) Experimental model for in vivo determination of dietary fibre and its effect on the absorption of nutrients in the small intestine. Br J Nutr 45:283–294

    Google Scholar 

  • Schmidt DG, Meijer RJ, Slangen CJ, Van Beresteijn EC (1995) Raising the pH of the pepsin-catalysed hydrolysis of bovine whey proteins increases the antigenicity of the hydrolysates. Clin Exp Allergy 25:1007–1017

    Google Scholar 

  • Schulten V, Lauer I, Scheurer S et al (2011) A food matrix reduces digestion and absorption of food allergens in vivo. Mol Nutr Food Res 55:1484–1491

    Google Scholar 

  • Sélo I, Clément G, Bernard H et al (1999) Allergy to bovine beta-lactoglobulin: specificity of human IgE to tryptic peptides. Clin Exp Allergy 29:1055–1063

    Google Scholar 

  • Sicherer SH, Sampson HA (2014) Food allergy: epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin Immunol 133:291–307

    Google Scholar 

  • Sipos T, Merkel JR (1970) An effect of calcium ions on the activity, heat stability, and structure of trypsin. Biochemistry 9:2766–2775

    Google Scholar 

  • Skripak JM, Matsui EC, Mudd K, Wood RA (2007) The natural history of IgE-mediated cow’s milk allergy. J Allergy Clin Immunol 120:1172–1177

    Google Scholar 

  • Sletten GBG, Holden L, Egaas E, Faeste CK (2008) Differential influence of the degree of processing on immunogenicity following proteolysis of casein and β-lactoglobulin. Food Agric Immunol 19:213–228

    Google Scholar 

  • Song Y, Wang J, Leung N et al (2015) Correlations between basophil activation, allergen-specific IgE with outcome and severity of oral food challenges. Ann Allergy Asthma Immunol 114:319–326

    Google Scholar 

  • Spuergin P, Mueller H, Walter M et al (1996) Allergenic epitopes of bovine alpha S1-casein recognized by human IgE and IgG. Allergy 51:306–312

    Google Scholar 

  • Stuart DI, Acharya KR, Walker NP et al (1986) Alpha-lactalbumin possesses a novel calcium binding loop. Nature 324:84–87

    Google Scholar 

  • Takagi K, Teshima R, Okunuki H, Sawada J (2003) Comparative study of in vitro digestibility of food proteins and effect of preheating on the digestion. Biol Pharm Bull 26:969–973

    Google Scholar 

  • Tang J (1963) Specificity of pepsin and its dependence on a possible “hydrophobicbinding site”. Nature 199:1094–1095

    Google Scholar 

  • Tang J (2013) Pepsin A. In: Handbook of proteolytic enzymes. ScienceDirect, pp 27–35

    Google Scholar 

  • Taylor SL, Hefle SL (2001) Will genetically modified foods be allergenic? J Allergy Clin Immunol 107:765–771

    Google Scholar 

  • Thomas K, Aalbers M, Bannon GA et al (2004) A multi-laboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins. Regul Toxicol Pharmacol 39:87–98

    Google Scholar 

  • Troost FJ, Steijns J, Saris WH, Brummer RJ (2001) Gastric digestion of bovine lactoferrin in vivo in adults. J Nutr 131:2101–2104

    Google Scholar 

  • Untersmayr E, Jensen-Jarolim E (2008) The role of protein digestibility and antacids on food allergy outcomes. J Allergy Clin Immunol 121:1301–1308

    Google Scholar 

  • Untersmayr E, Poulsen LK, Platzer MH et al (2005) The effects of gastric digestion on codfish allergenicity. J Allergy Clin Immunol 115:377–382

    Google Scholar 

  • Van Esch BCAM, Schouten B, de Kivit S et al (2011) Oral tolerance induction by partially hydrolyzed whey protein in mice is associated with enhanced numbers of Foxp3+ regulatory T-cells in the mesenteric lymph nodes. Pediatr Allergy Immunol 22:820–826

    Google Scholar 

  • Van Regenmortel MHV (1996) Mapping epitope structure and activity: from one-dimensional prediction to four-dimensional description of antigenic specificity. Methods 9:465–472

    Google Scholar 

  • Van Regenmortel MHV (1998) Mimotopes, continuous paratopes and hydropathic complementarity: novel approximations in the description of immunochemical specificity. J Dispers Sci Technol 19:1199–1219

    Google Scholar 

  • Van Regenmortel MHV (2009) What is a B-cell epitope? Methods Mol Biol 524:3–20

    Google Scholar 

  • Vieths S, Reindl J, Müller U et al (1999) Digestibility of peanut and hazelnut allergens investigated by a simple in vitro procedure. Eur Food Res Technol 209:379–388

    Google Scholar 

  • Villa C, Costa J, Oliveira MBPP, Mafra I (2018) Bovine milk allergens: a comprehensive review. Compr Rev Food Sci Food Saf 17:137–164

    Google Scholar 

  • Von Berg A (2009) Modified proteins in allergy prevention. In: Microbial host-interaction: tolerance versus allergy. Karger, Basel, pp 239–250

    Google Scholar 

  • Von Berg A (2013) Dietary interventions for primary allergy prevention - what is the evidence? World Rev Nutr Diet 108:71–78

    Google Scholar 

  • Wal J-M (2002) Cow’s milk proteins/allergens. Ann Allergy Asthma Immunol 89:3–10

    Google Scholar 

  • Wal JM, Bernard H, Créminon C et al (1995) Cow’s milk allergy: the humoral immune response to eight purified allergens. Adv Exp Med Biol 371B:879–881

    Google Scholar 

  • Wang J, Lin J, Bardina L et al (2010) Correlation of IgE/IgG4 milk epitopes and affinity of milk-specific IgE antibodies with different phenotypes of clinical milk allergy. J Allergy Clin Immunol 125:695–702

    Google Scholar 

  • Wickham M, Faulks R, Mills C (2009) In vitro digestion methods for assessing the effect of food structure on allergen breakdown. Mol Nutr Food Res 53:952–958

    Google Scholar 

  • Wróblewska B, Karamać M, Amarowicz R et al (2004) Immunoreactive properties of peptide fractions of cow whey milk proteins after enzymatic hydrolysis. Int J Food Sci Technol 39:839–850

    Google Scholar 

  • Yagami T, Haishima Y, Nakamura A et al (2000) Digestibility of allergens extracted from natural rubber latex and vegetable foods. J Allergy Clin Immunol 106:752–762

    Google Scholar 

  • Yamada C, Yamashita Y, Seki R et al (2006) Digestion and gastrointestinal absorption of the 14-16-kDa rice allergens. Biosci Biotechnol Biochem 70:1890–1897

    Google Scholar 

  • Yu W, Freeland DMH, Nadeau KC (2016) Food allergy: immune mechanisms, diagnosis and immunotherapy. Nat Rev Immunol 16:751–765

    Google Scholar 

  • Zdenek K, Jean-Claude M (2000) Infant formula containing sweet whey protein. Patent EP1048226A1

    Google Scholar 

  • Zeece M, Huppertz T, Kelly A (2008) Effect of high-pressure treatment on in-vitro digestibility of β-lactoglobulin. Innov Food Sci Emerg Technol 9:62–69

    Google Scholar 

  • Zheng H, Shen X, Bu G, Luo Y (2008) Effects of pH, temperature and enzyme-to-substrate ratio on the antigenicity of whey protein hydrolysates prepared by Alcalase. Int Dairy J 18:1028–1033

    Google Scholar 

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  1. Research Group for Food Allergy, National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark

    Katrine Lindholm Bøgh & Jeppe Madura Larsen

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  1. Katrine Lindholm Bøgh
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  2. Jeppe Madura Larsen
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Correspondence to Katrine Lindholm Bøgh .

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  1. School of Food and Nutritional Sciences, University College Cork, Cork, Cork, Ireland

    Alan L. Kelly

  2. Department of Food Science, Aarhus University, Aarhus, Denmark

    Lotte Bach Larsen

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Bøgh, K.L., Larsen, J.M. (2021). Reducing Allergenicity by Proteolysis. In: Kelly, A.L., Larsen, L.B. (eds) Agents of Change. Food Engineering Series. Springer, Cham. https://doi.org/10.1007/978-3-030-55482-8_19

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