Project
Dry heated cow’s milk protein and its immunogenicity
Physical and chemical changes of extensively dry heated cow’s milk protein and its immunogenicity.
Cow’s milk protein allergy (CMPA) is the one of the most commonly reported food allergies amongst all adverse reactions to food in infants and young children.(1) The manifestation of CMPA occurs within in the first 2 months of life and has been reported to affect < 1% children under the age of 2, in Europe.(2) In 50 % of IgE mediated CMP allergic children, CMPA is outgrown by the age of 3.(2,3) A strict allergen avoidance strategy is the most efficient therapy. However, this treatment leads to notable restrictions in live quality and requires other sources to guarantee an optimal nutritional sustenance of the infant.(4) In former studies, it has been observed that 75 % of CMP allergic children were able to tolerate “baked milk”. Moreover, 60 % of the baked milk tolerant patients were able to develop tolerance towards raw milk over a 5-years follow up period.(5,6) Baked milk is used as a term for CMP which is baked into a food matrix (e.g. muffins, waffels, and pizza cheese). However, the CMP and matrix used in prior studies is rather undefined. Moreover, very little is known about the physical and chemical changes occurring in the CMP during extensive dry heat treatment and how this correlates with the immunogenicity of the protein.
Aim
- Identification of physical and chemical changes in extensively dry
heated CMP
- Investigating the correlation between these changes and protein
digestion in an infant digestion model system
- Explain how the physical/chemical changes and the digestion products,
respectively, of dry heated CMP influence the immunogenicity of CMP
Approach
Heated CMP is investigated regarding its physical and chemical changes after extensive dry heating. This implies the degree of denaturation/aggregation as well as the formation of advanced glycation end products (AGE’s) and type of protein cross-linking. AGE’s and protein cross-linking is monitored using UHPLC-MS/MS(7,8) whilst denaturation/aggregation is investigated using a combination of methods including SDS-gelelectrophoresis(9), OPA-method, Ellman-method, Thioflavin-T-assay(10), and electron microscopic methods8. The effect of dry heated CMP on enzymatic proteolysis is crucial and will be considered when it comes to the investigations on the immunogenicity of the heated products in vitro.
References
(1) Rona, R. J.; Keil, T.; Summers, C.; Gislason, D.; Zuidmeer, L.; Sodergren, E.; Sigurdardottir, S. T.; Lindner, T.; Goldhahn, K.; Dahlstrom, J.; McBride, D.; Madsen, C. The prevalence of food allergy: a meta-analysis, The Journal of allergy and clinical immunology. 2007, 120, pp. 638–646.
(2) Schoemaker, A. A.; Sprikkelman, A. B.; Grimshaw, K. E.; Roberts, G.; Grabenhenrich, L.; Rosenfeld, L.; Siegert, S.; Dubakiene, R.; Rudzeviciene, O.; Reche, M.; Fiandor, A.; Papadopoulos, N. G.; Malamitsi-Puchner, A.; Fiocchi, A.; Dahdah, L.; Sigurdardottir, S. T.; Clausen, M.; Stanczyk-Przyluska, A.; Zeman, K.; Mills, E. N. C.; McBride, D.; Keil, T.; Beyer, K. Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort, Allergy. 2015, 70, pp. 963–972.
(3) Skripak, J. M.; Matsui, E. C.; Mudd, K.; Wood, R. A. The natural history of IgE-mediated cow's milk allergy, The Journal of allergy and clinical immunology. 2007, 120, pp. 1172–1177.
(4) Vandenplas, Y.; Koletzko, S.; Isolauri, E.; Hill, D.; Oranje, A. P.; Brueton, M.; Staiano, A.; Dupont, C. Guidelines for the diagnosis and management of cow's milk protein allergy in infants, Archives of disease in childhood. 2007, 92, pp. 902–908.
(5) Nowak-Wegrzyn, A.; Bloom, K. A.; Sicherer, S. H.; Shreffler, W. G.; Noone, S.; Wanich, N.; Sampson, H. A. Tolerance to extensively heated milk in children with cow's milk allergy, The Journal of allergy and clinical immunology. 2008, 122, 342-7, 347.e1-2.
(6) Kim, J. S.; Nowak-Wegrzyn, A.; Sicherer, S. H.; Noone, S.; Moshier, E. L.; Sampson, H. A. Dietary baked milk accelerates the resolution of cow's milk allergy in children, The Journal of allergy and clinical immunology. 2011, 128, 125-131.e2.
(7) Troise, A. D.; Fiore, A.; Roviello, G.; Monti, S. M.; Fogliano, V. Simultaneous quantification of amino acids and Amadori products in foods through ion-pairing liquid chromatography-high-resolution mass spectrometry, Amino acids. 2015, 47, pp. 111–124.
(8) Moeckel, U.; Duerasch, A.; Weiz, A.; Ruck, M.; Henle, T. Glycation Reactions of Casein Micelles, Journal of agricultural and food chemistry. 2016, 64, pp. 2953–2961.
(9) Vasbinder, A. J.; Alting, A. C.; Kruif, K. G. de Quantification of heat-induced casein–whey protein interactions in milk and its relation to gelation kinetics, Colloids and Surfaces B: Biointerfaces. 2003, 31, pp. 115–123.
(10) Raynes, J. K.; Day, L.; Crepin, P.; Horrocks, M. H.; Carver, J. A. Coaggregation of kappa-Casein and beta-Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils, Small (Weinheim an der Bergstrasse, Germany). 2017.
(1) Rona, R. J.; Keil, T.; Summers, C.; Gislason, D.; Zuidmeer, L.; Sodergren, E.; Sigurdardottir, S. T.; Lindner, T.; Goldhahn, K.; Dahlstrom, J.; McBride, D.; Madsen, C. The prevalence of food allergy: a meta-analysis, The Journal of allergy and clinical immunology. 2007, 120, pp. 638–646.
(2) Schoemaker, A. A.; Sprikkelman, A. B.; Grimshaw, K. E.; Roberts, G.; Grabenhenrich, L.; Rosenfeld, L.; Siegert, S.; Dubakiene, R.; Rudzeviciene, O.; Reche, M.; Fiandor, A.; Papadopoulos, N. G.; Malamitsi-Puchner, A.; Fiocchi, A.; Dahdah, L.; Sigurdardottir, S. T.; Clausen, M.; Stanczyk-Przyluska, A.; Zeman, K.; Mills, E. N. C.; McBride, D.; Keil, T.; Beyer, K. Incidence and natural history of challenge-proven cow's milk allergy in European children--EuroPrevall birth cohort, Allergy. 2015, 70, pp. 963–972.
(3) Skripak, J. M.; Matsui, E. C.; Mudd, K.; Wood, R. A. The natural history of IgE-mediated cow's milk allergy, The Journal of allergy and clinical immunology. 2007, 120, pp. 1172–1177.
(4) Vandenplas, Y.; Koletzko, S.; Isolauri, E.; Hill, D.; Oranje, A. P.; Brueton, M.; Staiano, A.; Dupont, C. Guidelines for the diagnosis and management of cow's milk protein allergy in infants, Archives of disease in childhood. 2007, 92, pp. 902–908.
(5) Nowak-Wegrzyn, A.; Bloom, K. A.; Sicherer, S. H.; Shreffler, W. G.; Noone, S.; Wanich, N.; Sampson, H. A. Tolerance to extensively heated milk in children with cow's milk allergy, The Journal of allergy and clinical immunology. 2008, 122, 342-7, 347.e1-2.
(6) Kim, J. S.; Nowak-Wegrzyn, A.; Sicherer, S. H.; Noone, S.; Moshier, E. L.; Sampson, H. A. Dietary baked milk accelerates the resolution of cow's milk allergy in children, The Journal of allergy and clinical immunology. 2011, 128, 125-131.e2.
(7) Troise, A. D.; Fiore, A.; Roviello, G.; Monti, S. M.; Fogliano, V. Simultaneous quantification of amino acids and Amadori products in foods through ion-pairing liquid chromatography-high-resolution mass spectrometry, Amino acids. 2015, 47, pp. 111–124.
(8) Moeckel, U.; Duerasch, A.; Weiz, A.; Ruck, M.; Henle, T. Glycation Reactions of Casein Micelles, Journal of agricultural and food chemistry. 2016, 64, pp. 2953–2961.
(9) Vasbinder, A. J.; Alting, A. C.; Kruif, K. G. de Quantification of heat-induced casein–whey protein interactions in milk and its relation to gelation kinetics, Colloids and Surfaces B: Biointerfaces. 2003, 31, pp. 115–123.
(10) Raynes, J. K.; Day, L.; Crepin, P.; Horrocks, M. H.; Carver, J. A. Coaggregation of kappa-Casein and beta-Lactoglobulin Produces Morphologically Distinct Amyloid Fibrils, Small (Weinheim an der Bergstrasse, Germany). 2017.