Can Glycation Reduce Food Allergenicity? Qinchun Rao, Xingyi Jiang

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Can Glycation Reduce Food Allergenicity? Qinchun Rao, Xingyi Jiang, Yida Li, Mustafa Samiwala, and Theodore P. Labuza J. Agric. Food Chem., Just Accepted Manuscript • DOI: 10.1021/acs.jafc.8b00660 • Publication Date (Web): 16 Apr 2018 Downloaded from http://pubs.acs.org on April 16, 2018

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Journal of Agricultural and Food Chemistry

Can Glycation Reduce Food Allergenicity?

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Qinchun Rao,*,† Xingyi Jiang,* Yida Li,# Mustafa Samiwala,* and Theodore P. Labuza#

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*

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Florida 32306, USA

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#

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Department of Nutrition, Food and Exercise Sciences, Florida State University, Tallahassee,

Department of Food Science and Nutrition, University of Minnesota, St. Paul, Minnesota 55108,

USA

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Corresponding Author. Tel: +1 850-644-8215. Fax: +1 850-645-5000. Email: [email protected]

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Abstract

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As a naturally occurring reaction during food processing, glycation, also known as non-

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enzymatic browning or Maillard reaction, can improve food protein physiochemical properties

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and functionality. In this perspective, three aspects of glycation (terminology confusion between

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glycation and glycosylation, its current application, and its impact on immunoreactivity) are

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elaborated. Overall, the immunoreactivity of glycated proteins may decrease, remain unchanged,

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or even increase after food glycation. Also, it should be noted that the effect of glycation on the

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immunoglobulin (Ig)E- or IgG-binding capacity of allergens do not necessarily and correctly

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predict the allergenicity of the glycated protein in the allergic patient population.

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Keywords: glycation, Maillard reaction, allergenicity, immunoreactivity

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Introduction Currently, there is no approved treatment for food allergy which can only be managed by

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strict dietary avoidance and treatment of symptoms.1 To identify an unknown food allergy, the

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recommended method is in vivo clinical diagnostic tests such as skin prick test and oral food

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challenges, which usually take place after the allergenic symptoms have occurred.2 However,

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these in vivo tests are inconvenient, expensive, and time-consuming. More seriously, these

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diagnostic tests may induce severe and potential life-threatening allergic reactions in patients.2

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To reduce the risk of food allergy, the U.S. food manufacturers have been required to

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label food allergens or ingredients derived from eight major allergenic foods (i.e., egg, milk,

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peanut, tree nuts, fish, shellfish, soy, and wheat) since 2006.3 To better comply with the food

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regulations, in general, the food industry can use two prevention strategies. First, different food

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processing techniques have the potential to reduce the allergenicity of food products, which has

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been reviewed comprehensively.4 Protein glycation is one of these food-processing techniques.

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Second, many immunoglobulin (Ig)E- or IgG-based analytical methods have been used to study

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the effect of different processing techniques on the immunoreactivity of allergenic proteins and

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to detect those undeclared allergenic residues in foods. In this perspective, three aspects of

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glycation (terminology confusion between glycation and glycosylation, its current application,

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and its impact on immunoreactivity) are elaborated.

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Terminology Confusion of Food Protein Glycation Historically, the definition of glycation has been revised at least three times by the

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International Union of Pure and Applied Chemistry (IUPAC) and the International Union of

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Biochemistry (IUB) Joint Commission on Biochemical Nomenclature (JCBN). In 1985, the term

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“glycation” was suggested for “all reactions that link a sugar to a protein or peptide, whether or

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not catalyzed by an enzyme.”5 In 1986, the second half of this statement was revised to “whether

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or not they form a glycosyl bond.”6 In order to distinguish protein glycation from protein

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glycosylation (i.e., the enzymatic-directed protein-carbohydrate interactions),7 its World Wide

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Web version from JCBN has been reworded by Dr. Gerard P. Moss (current Chairman of JCBN)

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to “all such reactions that link a sugar to a protein or peptide,” in which the term “such reactions”

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means non-enzymatic reactions.8 It has been reported that although both glycation and

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glycosylation are not random reactions, glycation is less specific than glycosylation.9

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Despite they are two completely different concepts, the term “glycosylation” has been

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misused in many peer-reviewed studies of various glycated food proteins such as whey proteins10

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and codfish parvalbumin.11 In addition, many research articles complex this term by defining it

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as “non-enzymatic glycosylation”12 and “Maillard-type protein-polysaccharide conjugation.”13

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Overall, this inappropriate terminology usage should be avoided in related research in the future.

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Accuracy and consistency in the use of scientific terms would not only help avoid

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misunderstanding but also improve interdisciplinary communication.

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Application of Glycation and Its Impact on Food Protein Immunoreactivity Food protein glycation, also known as non-enzymatic browning or Maillard reaction, is a

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chemical reaction between an available amino group (usually from proteins) and a carbonyl-

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containing moiety (reducing sugar). A reversible Schiff base is initially formed between a

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reducing sugar and the amino group. The Schiff base undergoes an intramolecular rearrangement

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to form the Amadori products.14 As a naturally occurring reaction during food processing, it has

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been reported that glycation can improve food protein physiochemical properties and

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functionality including solubility, emulsifying and foaming properties, antimicrobial activity, and

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thermal stability.13, 15 Although the glycated food proteins have received much attention in recent

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years, to the best of our knowledge, the commercial glycated food products are still not available.

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Currently, all research and development of food glycation technology are only at the

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laboratory scale. In general, the lab-scale glycation can be classified into two methods: the dry

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method and the wet method. In the dry method, the glycated proteins can be produced during

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storage of the freeze-dried powders of protein-sugar mixtures under an elevated temperature and

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a given relative humidity (Table 1). In the wet method, the glycated proteins can be lyophilized

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after storage of the liquid mixture of protein and reducing sugar under elevated temperature

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(Table 1).

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It is noted that many in vitro (Table 1) and in vivo (Table 2) studies have shown that the

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immunoreactivity of glycated proteins may decrease, remain unchanged, or even increase after

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food glycation. This indicates that protein glycation has the ability to generate new epitopes

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(linear or conformational) and/or change the conformation of existing epitopes recognized by

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IgE and/or IgG antibodies. For example, it has been reported that the conformational change in

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epitopes on glycated hen egg ovalbumin decreased the IgE-binding capacity, simultaneously,

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increased the in vitro immunoreactivity of IgG.16

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The effect of glycation on the protein immunoreactivity is also dependent on a number of

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factors mainly including sources of protein and sugar,17 protein-to-sugar ratio,18 and processing

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conditions (dry or wet methods, temperature, and incubation time).19 For example, the increase

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in the glycation incubation time could not guarantee the reduction of immunoreactivity.18 It

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should be noted that there are few studies being conducted to compare the yield efficiency and

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the immunoreactivity difference between two preparation methods (dry and wet) using the same

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protein. It has been reported that the antigenicity of the wet-heated soy protein isolate (SPI)

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decreased much greater than that of the dry-heated SPI.20 However, this might be caused by the

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difference in the processing conditions and the protein-to-sugar ratios between these two

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methods.

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In addition, there are two major challenges in the study of the effect of glycation on food protein immunoreactivity. First, a simple and effective quantitative analysis method to measure

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the yield of the glycated proteins is needed. Currently, the glycated proteins are mainly

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illustrated by the smearing effect using sodium dodecyl sulfate-polyacrylamide gel

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electrophoresis (SDS-PAGE) due to the change in protein molecular weight (Tables 1 and 2).

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However, the smearing effect may be generated by protein aggregation during glycation. Also,

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although glycation can be indirectly confirmed by the measurement of browning products at 420

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nm,18 it should be noted that this Maillard-induced color change can be developed due to the

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trace amount of the inherent reducing sugar.21

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Second, in vivo studies of food protein glycation are limited (Table 2). Most published

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studies are in vitro (Table 1). However, the effect of food protein glycation on the IgE- or IgG-

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binding capacity of allergens do not necessarily and correctly predict the allergenicity of the

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glycated protein in the allergic patient population. More importantly, as mentioned by the

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European Food Safety Authority (EFSA) recently, “most studies available report on the IgE-

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binding capacity of processed foods rather than on their allergenicity, whereas systematic

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investigations on the effects of food processing on allergenicity under controlled conditions are

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scarce.”22

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Acknowledgements

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This study was supported in part by the Midwest Dairy Association and by the National Institute of Food and Agriculture, U.S. Department of Agriculture (2017-70001-25984).

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Table 1. Effect of glycation on the in vitro immunoreactivity of various food proteins Food protein

Reducing sugar

Atlantic cod parvalbumin

Glucose

Bovine β-lactoglobulin

Galactose

1:1

10-kDa dextran

1:2

20-kDa dextran

1:2

Bovine whey protein isolate

Glucose

0.17-7.83:1

Buckwheat Fag e 1

20-kDa arabinogalactan 1.4-kDa xyloglucan Glucose Ribose

1:1

Glucose

Hazelnut Cor a 11

Hen egg ovalbumin

Glucose

Protein: sugar (w/w) 1:5 (molar ratio)

Glycation conditions Temp. Matrix (°C) Liquid 60

Immunoreactivity Time 5-48 h

Powder (RH44%) Powder (RH44%) Powder (RH44%) Powder (RH79%)

40

1d

60

36 h

60

60 h

40-60

24-120 h

60

7d

1:18 1:15

Powder (RH65%) Liquid Liquid

100 100

30 min 30 min

1:2

Powder

37

7d

25:21

Liquid

60 145 60

3d 20 min 0-2 h

1:0.05

Powder (RH65%) Powder (RH65%)

50

48-96 h

50

48-96 h

100

2h

Hen egg ovomucoid

Glucose

1:0.05

Peanut 2S albumins (Ara h 2/6)

Glucose

1:4.5

Liquid

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Glycation degree

• Higher molecular weight bands on reducing SDSPAGE • Reduction of lysine content • Highly glycated • Non-aggregated • Maximum level of glycation • Low aggregation • Maximum level of glycation • Low aggregation • Absorbance increase at 420 nm • Decrease in free amino acid content • Broad bands on reducing SDS-PAGE • Weak and diffused protein band on reducing SDSPAGE • Smear bands on reducing SDS-PAGE • Decrease in free amino acid content

• Decrease of free amino acid group • Covalent aggregation on non-reducing SDS-PAGE • Diffuse bands at high molecular weight on nonreducing SDS-PAGE • Decrease in free amino acid content N/A

IgG



IgE

References



11



23

↑ × 18







24

↓ ↓ 19

×

×

↓ ↓ ↑

↓ ↓ ↓





25





25



26

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Food protein

Reducing sugar

Scallop tropomyosin

Glucose

Protein: sugar (w/w) 1:540

Ribose Maltose Maltotriose Ribose

1: 450 1:1027 1:1513 1:450

Fructooligosaccharides (FOS)

Squid tropomyosin Soy protein isolate

Immunoreactivity Time 48 h

Glycation degree

IgG

Powder (RH35%)

60

1:1.1

Powder (RH65%)

60

0-19 d

Fructose

1:0.07

60

0-19 d

FOS

1:4-74 (molar ratio) 1:1.3-24 (molar ratio)

Powder (RH65%) Liquid

95

0-5 h



Liquid

95

0-5 h



• Reduction of lysine content • Smear bands on reducing SDS-PAGE • Invisible 7S and 11S fractions on SDS-PAGE • A significant decrease in free amino acid groups • Decrease in free amino acid content

IgE ↑

• Smear bands on SDS-PAGE • Reduction of lysine content

3h 15 d 15 d 3h

Fructose

120 121

Glycation conditions Temp. Matrix (°C) Powder 60 (RH35%)

↑ ↑ × ↓



References 17

27

20



RH: relative humidity; ↑: increase; ↓: decrease; ×: unchanged; N/A: not available; d: day; h: hour; min: minute; w: week; SDS-PAGE: sodium dodecyl sulfate polyacrylamide gel electrophoresis

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Table 2. Effect of glycation on the in vivo allergenicity of hen egg ovalbumin

Reducing Sugar Glucose

Mannose Glucomanna

123

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Glycation conditions Protein:sugar Temp. Matrix (w/w) (°C) 1:4003 Liquid 50

Time

1:4003

Liquid

1:1

Powder (RH65%)

Glycation degree

Mouse model

Allergenicity

6w

• Diffuse bands on reducing SDS-PAGE

C57BL/6J(B6)



50

6w

• Diffuse bands on nonreducing SDS-PAGE

BALB/c



55

72 h

• Higher molecular weight bands on reducing SDS-PAGE • Decrease of free amino acids

BALB/c



RH: relative humidity; ↑: increase; ↓: decrease; h: hour; w: week

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Explanation

• Scavenger receptor class A type-1 and type-2 targets glycated OVA to the MHC class Ⅱ loading pathway in myeloid dendritic cell • Glycation enhanced the activation of OVA-specific CD4+ T cells • Glycan structure (pyraline-OVA) can bind to scavenger receptor class A, which enhanced the activation of OVAspecific CD4+ T cells • Regulation of dendritic cells differentiation and T-cell activation • Reduction of type-1 and type-2 immune response

References 28

29

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References

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1. Vierk, K. A.; Koehler, K. M.; Fein, S. B.; Street, D. A., Prevalence of self-reported food allergy in American adults and use of food labels. J. Allergy Clin. Immunol. 2007, 119, 15041510. 2. Boyce, J. A.; Assa'ad, A.; Burks, A. W.; Jones, S. M.; Sampson, H. A.; Wood, R. A.; Plaut, M.; Cooper, S. F.; Fenton, M. J.; Arshad, S. H.; Bahna, S. L.; Beck, L. A.; ByrdBredbenner, C.; Camargo, C. A.; Eichenfield, L.; Furuta, G. T.; Hanifin, J. M.; Jones, C.; Kraft, M.; Levy, B. D.; Lieberman, P.; Luccioli, S.; McCall, K. M.; Schneider, L. C.; Simon, R. A.; Simons, F. E. R.; Teach, S. J.; Yawn, B. P.; Schwaninger, J. M., Guidelines for the diagnosis and management of food allergy in the United States: Report of the NIAID-Sponsored Expert Panel. J. Allergy Clin. Immunol. 2010, 126, S5-S58. 3. USFDA. Food Allergen Labeling and Consumer Protection Act of 2004. https://www.fda.gov/downloads/Food/GuidanceRegulation/UCM179394.pdf (April 13, 2018). 4. Verhoeckx, K. C.; Vissers, Y. M.; Baumert, J. L.; Faludi, R.; Feys, M.; Flanagan, S.; Herouet-Guicheney, C.; Holzhauser, T.; Shimojo, R.; van der Bolt, N., Food processing and allergenicity. Food Chem. Toxicol. 2015, 80, 223-240. 5. Sharon, N., IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycoproteins, glycopeptides and peptidoglycans. Recommendations 1985. Glycoconj. J. 1986, 3, 123-134. 6. Sharon, N., IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycoproteins, glycopeptides and peptidoglycans. Recommendations 1985. Eur. J. Biochem. 1986, 159, 1-6. 7. Brownlee, M.; Cerami, A.; Vlassara, H., Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N. Engl. J. Med. 1988, 318, 1315-1321. 8. Moss, G. P. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN). Nomenclature of glycoproteins, glycopeptides and peptidoglycans. Recommendations 1985. . http://www.chem.qmw.ac.uk/iupac/misc/noGreek/glycp.html (April 13, 2018). 9. Zhang, Q. B.; Ames, J. M.; Smith, R. D.; Baynes, J. W.; Metz, T. O., A perspective on the maillard reaction and the analysis of protein glycation by mass spectrometry: Probing the pathogenesis of chronic disease. J. Proteome Res. 2009, 8, 754-769. 10. Jimenez-Castano, L.; Villamiel, M.; Lopez-Fandino, R., Glycosylation of individual whey proteins by Maillard reaction using dextran of different molecular mass. Food Hydrocolloid 2007, 21, 433-443. 11. de Jongh, H. H. J.; Robles, C. L.; Timmerman, E.; Nordlee, J. A.; Lee, P. W.; Baumert, J. L.; Hamilton, R. G.; Taylor, S. L.; Koppelman, S. J., Digestibility and IgE-binding of glycosylated codfish parvalbumin. Biomed. Res. Int. 2013, doi:10.1155/2013/756789. 12. Mierzeiewska, D.; Mitrowska, P.; Rudnicka, B.; Kubicka, E.; Kostyra, H., Effect of nonenzymatic glycosylation of pea albumins on their immunoreactive properties. Food Chem. 2008, 111, 127-131. 13. Kato, A., Industrial applications of Maillard-type protein-polysaccharide conjugates. Food Sci. Technol. Res. 2002, 8, 193-199. 14. Hodge, J. E., Dehydrated foods: Chemistry of browning reactions in model systems. J. Agric. Food Chem. 1953, 1, 928-943. 15. Liu, J.; Ru, Q.; Ding, Y., Glycation a promising method for food protein modification: Physicochemical properties and structure, a review. Food Res. Int. 2012, 49, 170-183. 11 ACS Paragon Plus Environment

Journal of Agricultural and Food Chemistry

169 170 171 172 173 174 175 176 177 178 179 180 181 182 183 184 185 186 187 188 189 190 191 192 193 194 195 196 197 198 199 200 201 202 203 204 205 206 207 208 209 210 211 212

16. Ma, X. J.; Chen, H. B.; Gao, J. Y.; Hu, C. Q.; Li, X., Conformation affects the potential allergenicity of ovalbumin after heating and glycation. Food Addit. Contam. Part A Chem. Anal. Control Expo. Risk Assess 2013, 30, 1684-1692. 17. Nakamura, A.; Watanabe, K.; Ojima, T.; Ahn, D. H.; Saeki, H., Effect of Maillard reaction on allergenicity of scallop tropomyosin. J. Agric. Food Chem. 2005, 53, 7559-7564. 18. Bu, G. H.; Luo, Y. K.; Lu, J.; Zhang, Y., Reduced antigenicity of β-lactoglobulin by conjugation with glucose through controlled Maillard reaction conditions. Food Agr. Immunol. 2010, 21, 143-156. 19. Iwan, M.; Vissers, Y. M.; Fiedorowicz, E.; Kostyra, H.; Kostyra, E.; Savelkoul, H. F. J.; Wichers, H. J., Impact of Maillard reaction on immunoreactivity and allergenicity of the hazelnut allergen Cor a 11. J. Agric. Food Chem. 2011, 59, 7163-7171. 20. van de Lagemaat, J.; Manuel Silván, J.; Javier Moreno, F.; Olano, A.; Dolores del Castillo, M., In vitro glycation and antigenicity of soy proteins. Food Res. Int. 2007, 40, 153-160. 21. Li, Z.; Luo, Y. K.; Feng, L. G., Effects of Maillard reaction conditions on the antigenicity of α-lactalbumin and β-lactoglobulin in whey protein conjugated with maltose. Eur. Food Res. Technol. 2011, 233, 387-394. 22. EFSA NDA Panel (EFSA Panel on Dietetic Products Nutrition and Allergies), Scientific Opinion on the evaluation of allergenic foods and food ingredients for labelling purposes. EFSA Journal 2014, 12, 3894. doi:10.2903/j.efsa.2014.3894. 23. Corzo-Martinez, M.; Soria, A. C.; Belloque, J.; Villamiel, M.; Moreno, F. J., Effect of glycation on the gastrointestinal digestibility and immunoreactivity of bovine β-lactoglobulin. Int. Dairy J. 2010, 20, 742-752. 24. Nakamura, S.; Suzuki, Y.; Ishikawa, E.; Yakushi, T.; Jing, H.; Miyamoto, T.; Hashizume, K., Reduction of in vitro allergenicity of buckwheat Fag e 1 through the Maillard-type glycosylation with polysaccharides. Food Chem. 2008, 109, 538-545. 25. Jiménez-Saiz, R.; Belloque, J.; Molina, E.; López-Fandiño, R., Human immunoglobulin E (IgE) binding to heated and glycated ovalbumin and ovomucoid before and after in vitro digestion. J. Agric. Food Chem. 2011, 59, 10044-10051. 26. Vissers, Y. M.; Blanc, F.; Skov, P. S.; Johnson, P. E.; Rigby, N. M.; Przybylski-Nicaise, L.; Bernard, H.; Wal, J. M.; Ballmer-Weber, B.; Zuidmeer-Jongejan, L.; Szepfalusi, Z.; Ruinemans-Koerts, J.; Jansen, A. P. H.; Savelkoul, H. F. J.; Wichers, H. J.; Mackie, A. R.; Mills, C. E. N.; Adel-Patient, K., Effect of heating and glycation on the allergenicity of 2s albumins (Ara h 2/6) from peanut. PLoS ONE 2011, 6, doi:10.1371/journal.pone.0023998. 27. Nakamura, A.; Sasaki, F.; Watanabe, K.; Ojima, T.; Ahn, D. H.; Saeki, H., Changes in allergenicity and digestibility of squid tropomyosin during the Maillard reaction with ribose. J. Agric. Food Chem. 2006, 54, 9529-9534. 28. Ilchmann, A.; Burgdorf, S.; Scheurer, S.; Waibler, Z.; Nagai, R.; Wellner, A.; Yamamoto, Y.; Yamamoto, H.; Henle, T.; Kurts, C.; Kalinke, U.; Vieths, S.; Toda, M., Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: Role of macrophage scavenger receptor class A type I and II. J. Allergy Clin. Immunol. 2010, 125, 175-183. 29. Heilmann, M.; Wellner, A.; Gadermaier, G.; Ilchmann, A.; Briza, P.; Krause, M.; Nagai, R.; Burgdorf, S.; Scheurer, S.; Vieths, S.; Henle, T.; Toda, M., Ovalbumin modified with pyrraline, a Maillard reaction product, shows enhanced T-cell immunogenicity. J. Biol. Chem. 2014, 289, 7919-7928.

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Journal of Agricultural and Food Chemistry

30. Rupa, P.; Nakamura, S.; Katayama, S.; Mine, Y., Effects of ovalbumin glycoconjugates on alleviation of orally induced egg allergy in mice via dendritic-cell maturation and T-cell activation. Mol. Nutr. Food Res. 2014, 58, 405-417.

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