Can Mass Spectrometry Analysis of In Vitro Digestion Products Improve the Assessment of Allergenic Potential of a Newly Expressed Protein?

Authors

  • Rong Wang Bayer U.S. - CropScience, Chesterfield, MO
  • Norma Houston Corteva Agriscience™, Johnston, IA
  • Matthew L. Cheever BASF Corporation, Morrisville, NC https://orcid.org/0000-0001-5353-4880
  • Tao Geng Bayer U.S. - CropScience, Chesterfield, MO https://orcid.org/0000-0002-7367-4693
  • Nancy Gillikin BASF Corporation, Morrisville, NC
  • Justin McDonald Syngenta, Crop Protection, LLC., Research Triangle Park, NC
  • Hector Serrano BASF Corporation, Morrisville, NC
  • Jeffrey Shippar Eurofins Food Integrity and Innovation, Madison, WI https://orcid.org/0000-0003-1377-0541
  • Afua Tetteh BASF Corporation, Morrisville, NC
  • Yanfei Wang Bayer U.S. - CropScience, Chesterfield, MO
  • Lucy Liu Bayer U.S. - CropScience, Chesterfield, MO

DOI:

https://doi.org/10.21423/JRS-V09I1WANG

Keywords:

genetically modified crops, allergenicity assessment, in vitro digestion, mass spectrometry

Abstract

The rigorous safety assessment conducted on genetically modified crops includes an evaluation of allergenic potential for an associated newly expressed protein (NEP). Since no single method is recognized as a predictor for protein allergenicity, a weight of evidence approach (WOE) has been adopted. In vitro digestion is a part of the WOE approach and is used to evaluate the susceptibility of a NEP to digestion by gastrointestinal proteases. In 2017, the European Food Safety Authority outlined additional digestion conditions and suggested liquid chromatography tandem mass spectrometry (LC-MS/MS) as an analytical method to detect small post-digestion peptides. This technical review paper focuses on the question of whether LC-MS/MS can aid in assessing allergenic potential of in vitro digestion products generated under the newly proposed conditions. After an extensive review, it was determined that LC-MS/MS can detect very small digestion products. However, the method cannot provide relevant information to differentiate whether these products are allergenic or non-allergenic. Therefore, the use of LC-MS/MS for a standard in vitro digestibility assessment provides no improvement in allergenicity prediction.

doi: 10.21423/jrs-v09i1wang

References

Akkerdaas, J., Totis, M., Barnett, B., Bell, E., Davis, T., Edrington, T., Glenn, K., Graser, G., Herman, R., Knulst, A., Ladics, G., McClain, S., Poulsen, L. K., Ranjan, R., Rascle, J-B., Serrano, H., Speijer, D., Wang, R., Pereira Mouries, L., Capt, A., & van Ree, R. (2018). Protease resistance of food proteins: a mixed picture for predicting allergenicity but a useful tool for assessing exposure. Clinical and Translational Allergy, 8(1), 30. https://www.doi.org/10.1186/s13601-018-0216-9

Astwood, J. D., Leach, J. N., & Fuchs, R. L. (1996). Stability of food allergens to digestion in vitro. Nature Biotechnology, 14(10), 1269-1273. https://www.doi.org/10.1038/nbt1096-1269

Bogh, K. L., & Madsen, C. B. (2016). Food Allergens: Is There a Correlation between Stability to Digestion and Allergenicity? Critical Reviews in Food Science and Nutrition, 56(9), 1545-1567. https://www.doi.org/10.1080/10408398.2013.779569

Bracker, J., & Brockmeyer, J. (2018). Characterization and Detection of Food Allergens Using High-Resolution Mass Spectrometry: Current Status and Future Perspective. Journal of Agricultural and Food Chemistry, 66(34), 8935-8940. https://www.doi.org/10.1021/acs.jafc.8b02265

Canas, B., Lopez-Ferrer, D., Ramos-Fernandez, A., Camafeita, E., & Calvo, E. (2006). Mass spectrometry technologies for proteomics. Briefings in Functional Genomics & Proteomics, 4(4), 295-320. https://www.doi.org/10.1093/bfgp/eli002

Codex Alimentarius Commission. (2009). Foods derived from modern biotechnology, Second edition. Food and Agriculture Organization of the United Nations and World Health Organization, Rome. Retrieved from http://www.fao.org/3/a-a1554e.pdf

Colgrave, M. L., Byrne, K., Pillai, S. V., Dong, B., Leonforte, A., Caine, J., Kowalczyk, L., Scoble, J. A., Petrie, J. R., Singh, S., & Zhou, X-R. (2019). Quantitation of seven transmembrane proteins from the DHA biosynthesis pathway in genetically engineered canola by targeted mass spectrometry. Food and Chemical Toxicology, 126, 313-321. https://www.doi.org/10.1016/j.fct.2019.02.035

Craft, G. E., Chen, A., & Nairn, A. C. (2013). Recent advances in quantitative neuroproteomics. Methods, 61(3), 186-218. https://www.doi.org/10.1016/j.ymeth.2013.04.008

Delaney, B., Astwood, J. D., Cunny, H., Conn, R. E., Herouet-Guicheney, C., MacIntosh, S., Meyer, L. S., Privalle, L., Gao, Y., Mattsson, J., Levine, M., & ILSI International Food Biotechnology Committee Task Force on Protein Safety. (2008). Evaluation of protein safety in the context of agricultural biotechnology. Food and Chemical Toxicology, 46(Supplement 2), S71-S97. https://www.doi.org/10.1016/j.fct.2008.01.045

Ewing, N. P., & Cassady, C. J. (2001). Dissociation of multiply charged negative ions for hirudin (54-65), fibrinopeptide B, and insulin A (oxidized). Journal of the American Society for Mass Spectrometry, 12(1), 105-116. https://www.doi.org/10.1016/s1044-0305(00)00195-1

Fernandez, A., Mills, E. N. C., Koning, F., & Moreno, F. J. (2019). Safety Assessment of Immune-Mediated Adverse Reactions to Novel Food Proteins. Trends in Biotechnology, 37(8), P796-800. https://www.doi.org/10.1016/j.tibtech.2019.03.010

Fricker, L. D. (2015). Limitations of Mass Spectrometry-Based Peptidomic Approaches. Journal of the American Society for Mass Spectrometry, 26(12), 1981-1991. https://www.doi.org/10.1007/s13361-015-1231-x

Fu, T-J., Abbott, U. R., & Hatzos, C. (2002). Digestibility of Food Allergens and Nonallergenic Proteins in Simulated Gastric Fluid and Simulated Intestinal Fluid - A Comparative Study. Journal of Agricultural and Food Chemistry, 50(24), 7154-1760. https://www.doi.org/10.1021/jf020599h

Grosvenor, A. J., Haigh, B. J., & Dyer, J. M. (2014). Digestion proteomics: tracking lactoferrin truncation and peptide release during simulated gastric digestion. Food & Function, 5(11), 2699-2705. https://www.doi.org/10.1039/c4fo00165f

Gundry, R. L., White, M. Y., Murray, C. I., Kane, L. A., Fu, Q., Stanley, B. A., & Van Eyk, J. E. (2009). Preparation of proteins and peptides for mass spectrometry analysis in a bottom-up proteomics workflow. Current Protocols in Molecular Biology, 90(1), 10.25.1-10.25.23. https://www.doi.org/10.1002/0471142727.mb1025s88

Herman, R. A., & Ladics, G. S. (2018). Allergenic sensitization versus elicitation risk criteria for novel food proteins. Regulatory Toxicology and Pharmacology, 94, 283-285. https://www.doi.org/10.1016/j.yrtph.2018.02.016

Herman, R. A., Woolhiser, M. M., Ladics, G. S., Korjagin, V. A., Schafer, B. W., Storer, N. P., Green, S. B., & Kan, L. (2007). Stability of a set of allergens and non-allergens in simulated gastric fluid. International Journal of Food Sciences and Nutrition, 58(2), 125-141. https://www.doi.org/10.1080/09637480601149640

Kaneko, N., Nakamura, A., Washimi, Y., Kato, T., Sakurai, T., Arahata, Y., Bundo, M., Takeda, A., Niida, S., Ito, K., Toba, K., Tanaka, K., & Yanagisawa, K. (2014). Novel plasma biomarker surrogating cerebral amyloid deposition. Proceedings of the Japan Academy, Series B, 90(9), 353-364. https://www.doi.org/10.2183/pjab.90.353

Korte, R., & Brockmeyer, J. (2017). Novel mass spectrometry approaches in food proteomics. TrAC Trends in Analytical Chemistry, 96, 99-106. https://www.doi.org/10.1016/j.trac.2017.07.010

Lakbub, J. C., Shipman, J. T., & Desaire, H. (2018). Recent mass spectrometry-based techniques and considerations for disulfide bond characterization in proteins. Analytical and Bioanalytical Chemistry, 410(10), 2467-2484. https://www.doi.org/10.1007/s00216-017-0772-1

Lam, H. (2011). Building and searching tandem mass spectral libraries for peptide identification. Molecular and Cellular Proteomics, 10(12), R111.008565. https://www.doi.org/10.1074/mcp.R111.008565

Liu, Y., Qing, H., & Deng, Y. (2014). Biomarkers in Alzheimer's disease analysis by mass spectrometry-based proteomics. International Journal of Molecular Sciences, 15(5), 7865-7882. https://www.doi.org/10.3390/ijms15057865

Mamone, G., Picariello, G., Caira, S., Addeo, F., & Ferranti, P. (2009). Analysis of food proteins and peptides by mass spectrometry-based techniques. Journal of Chromatography A, 1216(43), 7130-7142. https://www.doi.org/10.1016/j.chroma.2009.07.052

Mann, M. (2019). The ever expanding scope of electrospray mass spectrometry - a 30 year journey. Nature Communications, 10(1), 3744. https://www.doi.org/10.1038/s41467-019-11747-z

Metcalfe, D. D., Astwood, J. D., Townsend, R., Sampson, H. A., Taylor, S. L., & Fuchs, R. L. (1996). Assessment of the allergenic potential of foods derived from genetically engineered crop plants. Critical Reviews in Food Science and Nutrition, 36 Suppl, S165-186. https://www.doi.org/10.1080/10408399609527763

Naegeli, H., Birch, A. N., Casacuberta, J., De Schrijver, A., Gralak, M. A., Guerche, P., Jones, H., Manachini, B., Messean, A., Nielsen, E. E., Nogue, F., Robaglia, C., Rostoks, N., Sweet, J., Tebbe, C., Visioli, F., Wal, J-M., Eigenmann, P., Epstein, M., Hoffmann-Sommergruber, K., Koning, F., Lovik, M., Mills, C., Moreno, F. J., van Loveren, H., Selb, R., & Fernandez Dumont, A. (2017). Guidance on allergenicity assessment of genetically modified plants. EFSA Journal, 15(6), e04862. https://www.doi.org/10.2903/j.efsa.2017.4862

Organisation for Economic Co-operation and Development. (1993). Safety Evaluation of Foods Derived by Modern Biotechnology: Concepts and Principles. Retrieved from http://www.oecd.org/env/ehs/biotrack/41036698.pdf

Picariello, G., Mamone, G., Nitride, C., Addeo, F., & Ferranti, P. (2013). Protein digestomics: Integrated platforms to study food-protein digestion and derived functional and active peptides. TrAC Trends in Analytical Chemistry, 52, 120-134. https://www.doi.org/10.1016/j.trac.2013.08.001

Piper, D. W., & Fenton, B. H. (1965). pH stability and activity curves of pepsin with special reference to their clinical importance. Gut, 6(5), 506-508. https://www.doi.org/10.1136/gut.6.5.506

Porras-Yakushi, T. R., Sweredoski, M. J., & Hess, S. (2015). ETD Outperforms CID and HCD in the Analysis of the Ubiquitylated Proteome. Journal of the American Society for Mass Spectrometry, 26(9), 1580-1587. https://www.doi.org/10.1007/s13361-015-1168-0

Roepstorff, P., & Fohlman, J. (1984). Proposal for a common nomenclature for sequence ions in mass spectra of peptides. Biomedical Mass Spectrometry, 11(11), 601. https://www.doi.org/10.1002/bms.1200111109

Schnell, S., & Herman, R. A. (2009). Should digestion assays be used to estimate persistence of potential allergens in tests for safety of novel food proteins?. Clinical and Molecular Allergy, 7(1), 1-7. https://www.doi.org/10.1186/1476-7961-7-1

Schrader, M., Schulz-Knappe, P., & Fricker, L. D. (2014). Historical perspective of peptidomics. EuPA Open Proteomics, 3, 171-182. https://www.doi.org/10.1016/j.euprot.2014.02.014

Shen, Y., Tolic, N., Xie, F., Zhao, R., Purvine, S. O., Schepmoes, A. A., Moore, R. J., Anderson, G. A., & Smith, R. D. (2011). Effectiveness of CID, HCD, and ETD with FT MS/MS for Degradomic-Peptidomic Analysis: Comparison of Peptide Identification Methods. Journal of Proteome Research, 10(9), 3929-3943. https://www.doi.org/10.1021/pr200052c

Slechtova, T., Gilar, M., Kalikova, K., & Tesarova, E. (2015). Insight into Trypsin Miscleavage: Comparison of Kinetic Constants of Problematic Peptide Sequences. Analytical Chemistry, 87(15), 7636-7643. https://www.doi.org/10.1021/acs.analchem.5b00866

Tang, L. (2018). Next-generation peptide sequencing. Nature Methods, 15(12), 997. https://www.doi.org/10.1038/s41592-018-0240-7

Taulier, N., & Chalikian, T. V. (2001). Characterization of pH-induced transitions of β-lactoglobulin: ultrasonic, densimetric, and spectroscopic studies. Journal of Molecular Biology, 314(4), 873-889. https://www.doi.org/10.1006/jmbi.2001.5188

Thomas, K., Aalbers, M., Bannon, G. A., Bartels, M., Dearman, R. J., Esdaile, D. J., Fu, T. J., Glatt, C. M., Hadfield, N., Hatzos, C., Hefle, S. L., Heylings, J. R., Goodman, R. E., Henry, B., Herouet, C., Holsapple, M., Ladics, G. S., Landry, T. D., MacIntosh, S. C., Rice, E. A., Privalle, L. S., Steiner, H. Y., Teshima, R., van Ree, R., Woolhiser, M., & Zawodny, J. (2004). A multi-laboratory evaluation of a common in vitro pepsin digestion assay protocol used in assessing the safety of novel proteins. Regulatory Toxicology and Pharmacology, 39(2), 87-98. https://www.doi.org/10.1016/j.yrtph.2003.11.003

Torcello-Gomez, A., Dupont, D., Jardin, J., Briard-Bion, V., Deglaire, A., Risse, K., Mechoulan, E., & Mackie, A. (2020). The pattern of peptides released from dairy and egg proteins is highly dependent on the simulated digestion scenario. Food & Function, 11(6), 5240-5256. https://www.doi.org/10.1039/D0FO00744G

Verhoeckx, K., Bogh, K. L., Dupont, D., Egger, L., Gadermaier, G., Larre, C., Mackie, A., Mednard, O., Adel-Patient, K., Picariello, G., Portmann, R., Smit, J., Turner, P., Untersmayr, E., & Epstein, M. M. (2019). The relevance of a digestibility evaluation in the allergenicity risk assessment of novel proteins. Opinion of a joint initiative of COST action ImpARAS and COST action INFOGEST. Food and Chemical Toxicology, 129, 405-423. https://www.doi.org/10.1016/j.fct.2019.04.052

Wang, R., Edrington, T. C., Storrs, S. B., Crowley, K. S., Ward, J. M., Lee, T. C., Liu, Z. L., Li, B., & Glenn, K. C. (2017). Analyzing pepsin degradation assay conditions used for allergenicity assessments to ensure that pepsin susceptible and pepsin resistant dietary proteins are distinguishable. PLoS One, 12(2). https://www.doi.org/10.1371/journal.pone.0171926

Wang, R., Wang, Y., Edrington, T. C., Liu, Z., Lee, T. C., Silvanovich, A., Moon, H. S., Liu, Z. L., & Li, B. (2020). Presence of small resistant peptides from new in vitro digestion assays detected by liquid chromatography tandem mass spectrometry: An implication of allergenicity prediction of novel proteins? PLoS One, 15(6), e0233745. https://www.doi.org/10.1371/journal.pone.

World Health Organization & Food and Agriculture Organization of the United Nations. (2001, January 22-25). Evaluation of Allergenicity of Genetically Modified Foods: Report of a Joint FAO/WHO Expert Consultation of Allergenicity of Foods Derived from Biotechnology. Food and Agriculture Organization of the United Nations, Rome. Retrieved from http://www.fao.org/fileadmin/templates/agns/pdf/topics/ec_jan2001.pdf0233745

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Published

2021-01-05

Issue

Vol. 9 No. 1 (2021): Special Issue on Genetically Modified Organisms

Section

Policy Commentaries

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Copyright (c) 2021 Rong Wang, Norma Houston, Matthew L. Cheever, Tao Geng, Nancy Gillikin , Justin McDonald, Hector Serrano, Jeffrey Shippar, Afua Tetteh, Yanfei Wang, Lucy Liu

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