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6. Modifying the infantʼs diet to prevent food allergy

Author

Grimshaw, Kate, Logan, Kirsty, OʼDonovan, Sinead, Kiely, Mairead, Patient, Karine, van Bilsen, Jolanda, Beyer, Kirsten, Campbell, Dianne E, Garcia-Larsen, Vanessa, Grabenhenrich, Linus, Lack, Gideon, Mills, Clare, Wal, Jean-Michel, and Roberts, Graham

Published
2017
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9. Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Author

Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H.H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E.M., Roggen, Erwin L., van Bilsen, Jolanda H.M., Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, Pharmacology, Icahn School of Medicine at Mount Sinai, Partenaires INRAE, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Universidade de Évora, Institute of Sciences of Food Production (ISPA), Consiglio Nazionale delle Ricerche (CNR), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Centro de Biotecnologia y Genomica de Plantas - Centre for Plant Biotechnology and Genomics, University of Belgrade, Utrecht University [Utrecht], Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Wageningen University and Research Centre (WUR), PAN, 3Rs Managing and Consulting ApS, TNO, COST Action [FA1402], European Commission, Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, and Pharmacology

Subjects
0301 basic medicine, Computer science, Iie-mediated food allergy, RAPID - Risk Analysis for Products in Development, Epithelial cells, Dendritic cells, sensitization, Allergic sensitization, 0302 clinical medicine, Life, Adverse Outcome Pathway, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Taverne, Allergies, Animal testing, Risk assessment, IgE-mediated food allergy, in vitro, In vitro models, Acquired immune system, 3. Good health, Health & Consumer Research, Biotechnology, Cells, Context (language use), Computational biology, 03 medical and health sciences, Adverse outcome pathway, T and B cells, Precursor frequency, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, AOP, Food, Health & Consumer Research, Nutrition, VLAG, B cells, food, Cellular pathways, Proteins, Adverse outcomes, In-vitro models, 030104 developmental biology, Immune system, 030228 respiratory system, Food, Food allergies, Cytology, Food sensitization, Food Science
Abstract

[Background] Before introducing proteins from new or alternative dietary sources into the market, a compressive risk assessment including food allergic sensitization should be carried out in order to ensure their safety. We have recently proposed the adverse outcome pathway (AOP) concept to structure the current mechanistic understanding of the molecular and cellular pathways evidenced to drive IgE-mediated food allergies. This AOP framework offers the biological context to collect and structure existing in vitro methods and to identify missing assays to evaluate sensitizing potential of food proteins. [Scope and approach] In this review, we provide a state-of-the-art overview of available in vitro approaches for assessing the sensitizing potential of food proteins, including their strengths and limitations. These approaches are structured by their potential to evaluate the molecular initiating and key events driving food sensitization. [Key findings and conclusions] The application of the AOP framework offers the opportunity to anchor existing testing methods to specific building blocks of the AOP for food sensitization. In general, in vitro methods evaluating mechanisms involved in the innate immune response are easier to address than assays addressing the adaptive immune response due to the low precursor frequency of allergen-specific T and B cells. Novel ex vivo culture strategies may have the potential to become useful tools for investigating the sensitizing potential of food proteins. When applied in the context of an integrated testing strategy, the described approaches may reduce, if not replace, current animal testing approaches., The authors are all part of the COST Action FA1402 entitled: Improving Allergy Risk Assessment Strategy for New Food Proteins (ImpARAS).

Published
2019

10. Nanomaterials and the Serosal Immune System in the Thoracic and Peritoneal Cavities

Author

Kuper, C Frieke, Pieters, Raymond H H, van Bilsen, Jolanda H M, IRAS OH Toxicology, dIRAS RA-1, IRAS OH Toxicology, and dIRAS RA-1

Subjects
0301 basic medicine, Adipose tissue, Review, lcsh:Chemistry, Serous Membrane, 0302 clinical medicine, Homeostasis, Innate lymphocytes, Lymphocytes, lcsh:QH301-705.5, Peritoneal Cavity, Spectroscopy, Innate lymphoid cell, General Medicine, Environmental exposure, Acquired immune system, Computer Science Applications, Serous fluid, medicine.anatomical_structure, 030220 oncology & carcinogenesis, SALC, Pleura, Serosa, medicine.symptom, Peritoneum, Pericardium, Thoracic Cavity, Inflammation, FALC, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Immune system, medicine, Animals, Humans, Physical and Theoretical Chemistry, Molecular Biology, business.industry, Organic Chemistry, MS, Nanostructures, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, Immune System, Immunology, business
Abstract

The thoracic and peritoneal cavities are lined by serous membranes and are home of the serosal immune system. This immune system fuses innate and adaptive immunity, to maintain local homeostasis and repair local tissue damage, and to cooperate closely with the mucosal immune system. Innate lymphoid cells (ILCs) are found abundantly in the thoracic and peritoneal cavities, and they are crucial in first defense against pathogenic viruses and bacteria. Nanomaterials (NMs) can enter the cavities intentionally for medical purposes, or unintentionally following environmental exposure; subsequent serosal inflammation and cancer (mesothelioma) has gained significant interest. However, reports on adverse effects of NM on ILCs and other components of the serosal immune system are scarce or even lacking. As ILCs are crucial in the first defense against pathogenic viruses and bacteria, it is possible that serosal exposure to NM may lead to a reduced resistance against pathogens. Additionally, affected serosal lymphoid tissues and cells may disturb adipose tissue homeostasis. This review aims to provide insight into key effects of NM on the serosal immune system.

Published
2021

14. Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation

Author

van Bilsen, Jolanda H M, Dulos, Remon, van Stee, Mariël F, Meima, Marie Y, Rouhani Rankouhi, Tanja, Neergaard Jacobsen, Lotte, Staudt Kvistgaard, Anne, Garthoff, Jossie A, Knippels, Léon M J, Knipping, Karen, Houben, Geert F, Verschuren, Lars, Meijerink, Marjolein, Krishnan, Shaji, Afd Pharmacology, Pharmacology, Afd Pharmacology, and Pharmacology

Subjects
lcsh:Immunologic diseases. Allergy, 0301 basic medicine, Test strategy, Immunology, Psychological intervention, text mining, Computational biology, Biology, 03 medical and health sciences, Child Development, 0302 clinical medicine, Immune system, Acquired immunodeficiency syndrome (AIDS), Cytochrome P-450 CYP1A2, medicine, Animals, Humans, early life, Immunology and Allergy, Gene Regulatory Networks, Original Research, Infant, Newborn, Computational Biology, Infant, biomarkers, FOXP3, Forkhead Transcription Factors, Immune modulation, medicine.disease, Early life, Disease Models, Animal, machine learning, 030104 developmental biology, Immune System Diseases, Immune System, immune networks, Chemokines, lcsh:RC581-607, 030215 immunology, Immune activation
Abstract

A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into prophylactic or therapeutic approaches, there is no regulatory guidance on how to assess the risk and benefit balance of such interventions. Six early life immune causal networks, each compromising a different time period in early life (the 1st, 2nd, 3rd trimester of gestations, birth, newborn, and infant period), were generated. Thereto information was extracted and structured from early life literature using the automated text mining and machine learning tool: Integrated Network and Dynamical Reasoning Assembler (INDRA). The tool identified relevant entities (e.g., genes/proteins/metabolites/processes/diseases), extracted causal relationships among these entities, and assembled them into early life-immune causal networks. These causal early life immune networks were denoised using GeneMania, enriched with data from the gene-disease association database DisGeNET and Gene Ontology resource tools (GO/GO-SLIM), inferred missing relationships and added expert knowledge to generate information-dense early life immune networks. Analysis of the six early life immune networks by PageRank, not only confirmed the central role of the “commonly used immune markers” (e.g., chemokines, interleukins, IFN, TNF, TGFB, and other immune activation regulators (e.g., CD55, FOXP3, GATA3, CD79A, C4BPA), but also identified less obvious candidates (e.g., CYP1A2, FOXK2, NELFCD, RENBP). Comparison of the different early life periods resulted in the prediction of 11 key early life genes overlapping all early life periods (TNF, IL6, IL10, CD4, FOXP3, IL4, NELFCD, CD79A, IL5, RENBP, and IFNG), and also genes that were only described in certain early life period(s). Concluding, here we describe a network-based approach that provides a science-based and systematical method to explore the functional development of the early life immune system through time. This systems approach aids the generation of a testing strategy for the safety and efficacy of early life immune modulation by predicting the key candidate markers during different phases of early life immune development.

Published
2020

15. Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation

Author

Afd Pharmacology, Pharmacology, van Bilsen, Jolanda H M, Dulos, Remon, van Stee, Mariël F, Meima, Marie Y, Rouhani Rankouhi, Tanja, Neergaard Jacobsen, Lotte, Staudt Kvistgaard, Anne, Garthoff, Jossie A, Knippels, Léon M J, Knipping, Karen, Houben, Geert F, Verschuren, Lars, Meijerink, Marjolein, Krishnan, Shaji, Afd Pharmacology, Pharmacology, van Bilsen, Jolanda H M, Dulos, Remon, van Stee, Mariël F, Meima, Marie Y, Rouhani Rankouhi, Tanja, Neergaard Jacobsen, Lotte, Staudt Kvistgaard, Anne, Garthoff, Jossie A, Knippels, Léon M J, Knipping, Karen, Houben, Geert F, Verschuren, Lars, Meijerink, Marjolein, and Krishnan, Shaji

Published
2020

16. Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?

Author

Castan, Laure, Bøgh, Katrine Lindholm, Maryniak, Natalia Zofia, Epstein, Michelle M, Kazemi, Sahar, O'Mahony, Liam, Bodinier, Marie, Smit, Joost J, van Bilsen, Jolanda H M, Blanchard, Carine, Głogowski, Robert, Kozáková, Hana, Schwarzer, Martin, Noti, Mario, de Wit, Nicole, Bouchaud, Grégory, Bastiaan-Net, Shanna, Castan, Laure, Bøgh, Katrine Lindholm, Maryniak, Natalia Zofia, Epstein, Michelle M, Kazemi, Sahar, O'Mahony, Liam, Bodinier, Marie, Smit, Joost J, van Bilsen, Jolanda H M, Blanchard, Carine, Głogowski, Robert, Kozáková, Hana, Schwarzer, Martin, Noti, Mario, de Wit, Nicole, Bouchaud, Grégory, and Bastiaan-Net, Shanna

Abstract

Significant efforts are necessary to introduce new dietary protein sources to feed a growing world population while maintaining food supply chain sustainability. Such a sustainable protein transition includes the use of highly modified proteins from side streams or the introduction of new protein sources that may lead to increased clinically relevant allergic sensitization. With food allergy being a major health problem of increasing concern, understanding the potential allergenicity of new or modified proteins is crucial to ensure public health protection. The best predictive risk assessment methods currently relied on are in vivo models, making the choice of endpoint parameters a key element in evaluating the sensitizing capacity of novel proteins. Here, we provide a comprehensive overview of the most frequently used in vivo and ex vivo endpoints in murine food allergy models, addressing their strengths and limitations for assessing sensitization risks. For optimal laboratory-to-laboratory reproducibility and reliable use of predictive tests for protein risk assessment, it is important that researchers maintain and apply the same relevant parameters and procedures. Thus, there is an urgent need for a consensus on key food allergy parameters to be applied in future food allergy research in synergy between both knowledge institutes and clinicians.

Published
2020

17. Functional regulatory immune responses against human cartilage glycoprotein-39 in health vs. proinflammatory responses in rheumatoid arthritis

Author

van Bilsen, Jolanda H.M., van Dongen, Henrike, Lard, Leroy R., van der Voort, Ellen I.H., Elferink, Dienne G., Bakker, Aleida M., Miltenburg, Andre M.M., Huizinga, Tom W.J., de Vries, Rene R.P., and Toes, Rene E.M.

Subjects
T cells -- Research, Science and technology
Abstract

The class of immune response against autoantigens could profoundly influence the onset and/or outcome of autoimmune diseases. Until now, there is only limited information on the antigen-specific balance between proinflammatory and regulatory responses in humans. Here we analyzed the natural immune response against a candidate autoantigen in rheumatoid arthritis, human cartilage glycoprotein-39 (HC gp-39). Peripheral blood mononuclear cells from healthy individuals reacted against HC gp-39 with the production of IL-10 but not IFN-[gamma]. Ex vivo assays indicated that the naturally occurring HC gp-39-specific immune response in bulk is powerful enough to suppress antigen-specific recall responses, demonstrating that rather than being unresponsive, the HC gp-39-directed immune response in healthy individuals shows a strong bias toward a regulatory phenotype. Moreover, [CD4.sup.+] T cell lines directed against HC gp-39 expressed CD25, glucocorticoid-induced tumor necrosis factor receptor, and Foxp3 molecules and were capable of suppressing antigen-specific T cell responses. Cell-cell contact was required for this suppression. As opposed to healthy individuals, the HC gp-39-directed immune response in 50% of patients with rheumatoid arthritis exhibits polarization toward a proinflammatory T helper 1 phenotype and is significantly less powerful in suppressing antigen-specific recall responses. Together these findings indicate that the presence of HC gp-39-specific immune responses in healthy individuals may have an inhibitory effect on inflammatory responses in areas where HC gp-39 is present. Furthermore, these data indicate that the class of HC gp-39-directed immune response in rheumatoid arthritis patients has shifted from an antiinflammatory toward a proinflammatory phenotype. regulatory T cells | autoantigen

Published
2004

18. Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies

Author

Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, Pharmacology, Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H.H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E.M., Roggen, Erwin L., van Bilsen, Jolanda H.M., Afd Pharmacology, dIRAS RA-1, One Health Toxicologie, Pharmacology, Lozano-Ojalvo, Daniel, Benedé, Sara, Antunes, Celia M., Bavaro, Simona L., Bouchaud, Grégory, Costa, Ana, Denery-Papini, Sandra, Díaz-Perales, Araceli, Garrido-Arandia, María, Gavrovic-Jankulovic, Marija, Hayen, Simone, Martínez-Blanco, Mónica, Molina, Elena, Monaci, Linda, Pieters, Raymond H.H., Villemin, Clelia, Wichers, Harry J., Wróblewska, Barbara, Willemsen, Linette E.M., Roggen, Erwin L., and van Bilsen, Jolanda H.M.

Published
2019

19. A network-based approach for identifying suitable biomarkers for oral immunotherapy of food allergy

Author

Sub IRAS Tox ITX (immunotoxicologie), Afd Pharmacology, One Health Toxicologie, dIRAS RA-1, Pharmacology, Van Bilsen, Jolanda H.M., Verschuren, Lars, Wagenaar, Laura, Vonk, Marlotte M., Van Esch, Betty C.A.M., Knippels, Léon M.J., Garssen, Johan, Smit, Joost J., Pieters, Raymond H.H., Van Den Broek, Tim J., Sub IRAS Tox ITX (immunotoxicologie), Afd Pharmacology, One Health Toxicologie, dIRAS RA-1, Pharmacology, Van Bilsen, Jolanda H.M., Verschuren, Lars, Wagenaar, Laura, Vonk, Marlotte M., Van Esch, Betty C.A.M., Knippels, Léon M.J., Garssen, Johan, Smit, Joost J., Pieters, Raymond H.H., and Van Den Broek, Tim J.

Published
2019

22. Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins?

Author

Castan, Laure, primary, Bøgh, Katrine L., additional, Maryniak, Natalia Z., additional, Epstein, Michelle M., additional, Kazemi, Sahar, additional, O'Mahony, Liam, additional, Bodinier, Marie, additional, Smit, Joost J., additional, van Bilsen, Jolanda H. M., additional, Blanchard, Carine, additional, Głogowski, Robert, additional, Kozáková, Hana, additional, Schwarzer, Martin, additional, Noti, Mario, additional, de Wit, Nicole, additional, Bouchaud, Grégory, additional, and Bastiaan‐Net, Shanna, additional

Published
2019
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23. The Impact of Immune Interventions: A Systems Biology Strategy for Predicting Adverse and Beneficial Immune Effects

Author

Meijerink, Marjolein, primary, van den Broek, Tim, additional, Dulos, Remon, additional, Neergaard Jacobsen, Lotte, additional, Staudt Kvistgaard, Anne, additional, Garthoff, Jossie, additional, Knippels, Léon, additional, Knipping, Karen, additional, Houben, Geert, additional, Verschuren, Lars, additional, and van Bilsen, Jolanda, additional

Published
2019
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24. Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

Author

van Bilsen, Jolanda H M, Sienkiewicz-Szłapka, Edyta, Lozano-Ojalvo, Daniel, Willemsen, Linette E. M., Antunes, Celia M, Molina, Elena, Smit, Joost J., Wróblewska, Barbara, Wichers, Harry J., Knol, Edward F., Ladics, Gregory S, Pieters, Raymond H. H., Denery-Papini, Sandra, Vissers, Yvonne M, Bavaro, Simona L, Larré, Colette, Verhoeckx, Kitty C M, Roggen, Erwin L, Afd Pharmacology, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-1, Afd Pharmacology, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-1, The Netherlands Organisation for Applied Scientific Research (TNO), University of Warmia and Mazury, Instituto de Investigación en Ciencias de la Alimentación (CIAL), Utrecht University [Utrecht], University of Evora, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Wageningen University and Research Center (WUR), University Medical Center [Utrecht], DuPont Company, Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Nestlé Research Center, Nestle Reasearch Center, Institute of Sciences of Food Production (ISPA), Consiglio Nazionale delle Ricerche (CNR), 3Rs Managing and Consulting ApS, and Wageningen University and Research [Wageningen] (WUR)

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, [SDV]Life Sciences [q-bio], Population, Immunology, Context (language use), Computational biology, Review, Sensitization, Food proteins, Allergic sensitization, 03 medical and health sciences, 0302 clinical medicine, Adverse outcome pathway, Food allergy, Adverse Outcome Pathway, Journal Article, Medicine, Immunology and Allergy, Mechanistic understanding, Animal testing, education, Tissue homeostasis, Food, Health & Consumer Research, VLAG, Key events, education.field_of_study, business.industry, RC581-607, medicine.disease, Key event relations, Molecular initiating event, 3. Good health, Food proteins, Molecular initiating event, 030104 developmental biology, medicine.anatomical_structure, Health & Consumer Research, Food, Immunologic diseases. Allergy, business, Mechanisticunderstanding, 030215 immunology
Abstract

[Background] The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP)., [Main body] The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell–cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential., [Conclusion] The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.org platform to expand the mechanistic data, improve the confidence in each of the proposed KE and key event relations (KERs), and allow for the identification of new, or refinement of established KE and KERs.

Published
2017

28. Abstracts from the Food Allergy and Anaphylaxis Meeting 2016

Author

Pouessel, Guillaume, Claverie, Claire, Labreuche, Julien, Renaudin, Jean-Marie, Dorkenoo, Aimée, Eb, Mireille, Moneret-Vautrin, Anne, Deschildre, Antoine, Leteurtre, Stephane, Grabenhenrich, Linus, Worm, Margitta, Dölle, Sabine, Scherer, Kathrin, Hutteger, Isidor, Christensen, Morten, Bindslev-Jensen, Carsten, Mortz, Charlotte, Eller, Esben, Kjaer, Henrik F, Carneiro-Leão, Leonor, Badas, Jenny, Coimbra, Alice, Levy, Dikla P, Ben-Shoshan, Moshe, Rimon, Ayelet, Benor, Shira, Arends, Nicolette J T, Edelbroek, Nikki, de Groot, Hans, Emons, Joyce A M, Brand, H. K A, Verhoeven, Dirk, van Veen, Leonieke N, de Jong, Nicolette W, Noh, Geunwoong, Jang, Eun H, Pascal, Mariona, Dominguez, Olga, Piquer, Mònica, Alvaro, Montserrat, Jimenez-Feijoo, Rosa, Lozano, Jaime, Machinena, Adriana, del Mar Folqué, Maria, Giner, Maria T, Plaza, Ana M, Turner, Paul, Patel, Nandinee, Vazquez-Ortiz, Marta, Lindsley, Sarah, Walker, Lucy, Rosenberg, Simon, Mari, Adriano, Alessandri, Claudia, Giangrieco, Ivana, Tuppo, Lisa, Rafaiani, Chiara, Mitterer, Georg, Ciancamerla, Michela, Ferrara, Rosetta, Bernardi, Maria L, Zennaro, Danila, Tamburrini, Maurizio, Ciardiello, Maria A, Harwanegg, Christian, Fernandez, Antonio, Selb, Regina, Egenmann, Philippe, Epstein, Michelle, Hoffmann-Sommergruber, Karin, Koning, Frits, Lovik, Martinus, Clare Mills, E. N, Moreno, Javier, van Loveren, Henk, Wal, Jean-Michel, Diesner, Susanne, Bergmayr, Cornelia, Pfitzner, Barbara, Assmann, Vera E, Starkl, Philipp, Endesfelder, David, Eiwegger, Thomas, Szepfalusi, Zsolt, Fehrenbach, Heinz, Jensen-Jarolim, Erika, Hartmann, Anton, Pali-Schöll, Isabella, Untersmayr, Eva, Wille, Soren, Meyer, Peter, Klingebiel, Caroline, Lidholm, Jonas, Ehrenberg, Angelica, Östling, Jonas, Cleach, Isabelle, Mège, Jean-Louis, Vitte, Joana, Aina, Roberta, Dubiela, Pawel, Pfeifer, Sabine, Bublin, Merima, Radauer, Christian, Humeniuk, Piotr, Kabasser, Stefan, Asero, Riccardo, Bogas, Gador, Gomez, Francisca, Campo, Paloma, Salas, Maria, Doña, Inmaculada, Barrionuevo, Esther, Guerrero, Maria A, Mayorga, Cristobalina, Prieto, Ana, Barber, Domingo, Torres, Maria J, Jamin, Annette, Wangorsch, Andrea, Ballmer, Barbara, Vieths, Stefan, Scheurer, Stephan, Apostolovic, Danijela, Mihailovic, Jelena, Krstic, Maja, Starkhammar, Maria, Velickovic, Tanja C, Hamsten, Carl, van Hage, Marianne, van Erp, Francine C, Knol, Edward F, Kansen, Hannah M, Pontoppidan, Bo, Meijer, Yolanda, van der Ent, Cornelis K, Knulst, André C, Sayers, Rebekah, Brown, Helen, Custovic, Adnan, Simpson, Angela, Mills, Claire, Schulz, Juliane, Akkerdaas, Jaap, Totis, Muriel, Capt, Annabelle, Herouet-Guicheney, Corinne, van Ree, Ronald, Banerjee, Tushar, Banerjee, Antima, Claude, Mathilde, Bouchaud, Grégory, Lupi, Roberta, Castan, Laure, Tranquet, Olivier, Denery-Papini, Sandra, Bodinier, Marie, Brossard, Chantal, De Poi, Rosella, Gritti, Elisa, De Dominicis, Emiliano, Popping, Bert, de Laureto, Patrizia P, Palosuo, Kati, Kukkonen, Anna K, Pelkonen, Anna, Mäkelä, Mika, Lee, Nanju A, Rost, Johanna, Muralidharan, Sridevi, Campbell, Dianne, Mehr, Sam, Nock, Catherine, Baumert, Joseph, Taylor, Steve, Mastrorilli, Carla, Tripodi, Salvatore, Caffarelli, Carlo, Perna, Serena, Di Rienzo Businco, Andrea, Sfika, Ifigenia, Dondi, Arianna, Bianchi, Annamaria, Dascola, Carlotta P, Ricci, Giampaolo, Cipriani, Francesca, Maiello, Nunzia, del Giudice, Michele M, Frediani, Tullio, Frediani, Simone, Macrì, Francesco, Pistoletti, Chiara, Iacono, Iride D, Patria, Maria F, Varin, Elena, Peroni, Diego, Comberiati, Pasquale, Chini, Loredana, Moschese, Viviana, Lucarelli, Sandra, Bernardini, Roberto, Pingitore, Giuseppe, Pelosi, Umberto, Olcese, Roberta, Moretti, Matteo, Cirisano, Anastasia, Faggian, Diego, Travaglini, Alessandro, Plebani, Mario, Verga, Maria C, Calvani, Mauro, Giordani, Paolo, Matricardi, Paolo M, Ontiveros, Noe, Cabrera-Chavez, Francisco, Galand, Julie, Beaudouin, Etienne, Pineau, Florence, Sakai, Shinobu, Matsunaga, Kayoko, Teshima, Reiko, Larré, Colette, Denery, Sandra, Tschirner, Sebastian, Trendelenburg, Valérie, Schulz, Gabriele, Niggemann, Bodo, Beyer, Kirsten, Bouferkas, Youcef, Belabbas, Younes, Saidi, Djamel, Kheroua, Omar, Mecherfi, Kamel E E, Guendouz, Malika, Haddi, Abir, Kaddouri, Hanane, Amaral, Luis, Pereira, Ana, Rodrigues, Susana, Datema, Mareen, Jongejan, Laurian, Clausen, Michael, Knulst, Andre, Papadopoulos, Nikolaos, Kowalski, Marek, de Blay, Frédéric, Zwinderman, Aeilko, Hoffman-Sommergruber, Karin, Ballmer-Weber, Barbara, Fernandez-Rivas, Montserrat, Deng, Shan, Yin, Jia, Eisenmann, Charlotte, Nassiri, Maria, Reinert, Rabea, van der Valk, Johanna P M, van Wijk, Roy G, Vergouwe, Yvonne, Steyerberg, Ewout W, Reitsma, Marit, Wichers, Harry J, Savelkoul, Huub F J, Vlieg-Boerstra, Berber, Dubois, Anthony E J, Carolino, Fabrícia, Rodolfo, Ana, Cernadas, Josefina, Roa-Medellín, Dasha, Rodriguez-Fernandez, Ana, Navarro, Joaquín, Albendiz, Vicente, Baeza, María L, Intente-Herrero, Sonsoles, Mikkelsen, Andrea, Mehlig, Kirsten, Lissner, Lauren, Verrill, Linda, Luccioli, Stefano, van Bilsen, Jolanda, Kuper, Frieke, Wolterbeek, André, Rankouhi, Tanja R, Verschuren, Lars, Cnossen, Hilde, Jeurink, Prescilla, Garssen, Johan, Knippels, Léon, Garthoff, Jossie, Houben, Geert, Leeman, Winfried, Eleonore Pettersson, M., Schins, Afke M M, 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Verhasselt, Valérie, Mrakovcic-Sutic, Ines, Banac, Srdan, Sutic, Ivana, Baricev-Novakovic, Zdenka, Sutic, Ingrid, Pavisic, Valentino, Muñoz-Cano, Rosa, Jiménez-Rodríguez, Teodoríkez, Corbacho, Daniel, Roca-Ferrer, Jordi, Bartra, Joan, Bulog, Aleksandar, Micovic, Vladimir, Markiewicz, Lidia, Szymkiewicz, Agata, Szyc, Anna, Wróblewska, Barbara, Harvey, Bryan M, Harthoorn, Lucien F, Wesley Burks, A., Rentzos, Georgios, Björk, Anna-Lena B, Bengtsson, Ulf, Barber, Colin, Kalicinsky, Chrystyna, Breynaert, Christine, Coorevits, Lieve, Jansen, Cornelia, Van Hoeyveld, Erna, Verbeke, Kristin, Kochuyt, Anne-Marie, Schrijvers, Rik, Deleanu, Diana, Muntean, Adriana, Konstantakopoulou, Maria, Pasioti, Maria, Papadopoulou, Anastasia, Iliopoulou, Anna, Mikos, Nikolaos, Kompoti, Evangelia, de Castro, Eunice D, Bartalomé, Borja, Ue, Kok L, Griffiths, Elizabeth, Till, Stephen, Grimshaw, Kate, Roberts, Graham, Selby, Anna, Butiene, Indre, Larco, Jose I, Dubakiene, Ruta, Fiandor, Ana, Fiocchi, Alessandro, Papadopoulos, Nikos, Sigurdardottir, Sigurveig, Sprikkelman, Aline, Schoemaker, Anne-Fleur, Xepapadaki, Paraskevi, Keil, Thomas, Cojocariu, Zizi, Barbado, Beatriz S, Iancu, Vasti, Arroabarren, Esozia, Esarte, Marta G, Arteaga, Miren, Andrade, Mayra C, Borges, Denise, Kalil, Jorge, Bianchi, Pedro G, Agondi, Rosana C, Gupta, Rinkesh K, Sharma, Akanksha, Gupta, Kriti, Das, Mukul, Dwivedi, Premendra, Karseladze, Rusudan, Jorjoliani, Liana, Saginadze, Lali, Tskhakaia, Mariam, Basello, Katia, Piuri, Gabriele, Speciani, Attilio F, Speciani, Michela C, Camerotto, Carla, Zinno, Francesco, Pakholchuk, Olga, Nedelska, Svitlana, Pattini, Stefano, Costantino, Maria T, Peveri, Silvia, Villalta, Danilo, Savi, Eleonora, Costanzi, Andrea, Revyakina, Vera A, Kiseleva, Marina A, Kuvshinova, Elena D, Larkova, Inna A, Shekhetov, Anton A, Silva, Diana, Moreira, André, Plácido, José, van der Kleij, Hanneke, van Twuijver, Esther, Sutorius, Robbert, de Kam, Pieter-Jan, van Odijk, Jenny, Lindqvist, Helen, Lustig, Elin, Jácome, Amyra A A, Aguilar, Karla L B, Domínguez, Miguel G, Hernández, David A M, Caruso, Cristiano, Casale, Cono, Rapaccini, Gian L, Romano, Antonino, De Vitis, Italo, Cocco, Renata R, Aranda, Carolina, Mallozi, Marcia C, Motta, Jackeline F, Moraes, Lilian, Pastorino, Antonio, Rosario, Nelson, Goudouris, Ekaterini, Porto, Arnaldo, Wandalsen, Neusa F, Sarinho, Emanuel, Sano, Flavio, Solé, Dirceu, Pitsios, Constantinos, Petrodimopoulou, Maria, Papadopoulou, Ekaterini, Passioti, Maria, Kontogianni, Meropi, Adamia, Nino, Khaleva, Ekaterina, del Prado, Ana P, Du Toit, George, Krzych, Edyta, Samolinska-Zawisza, Urszula, Furmanczyk, Konrad, Tomaszewska, Aneta, Raciborski, Filip, Lipiec, Agnieszka, Samel-Kowalik, Piotr, Walkiewicz, Artur, Borowicz, Jacek, Samolinski, Boleslaw, Nano, Aimee L, Recto, Marysia, Somoza, Maria L, López, Natalia B, Alzate, Diana P, Ruano, Francisco J, Garcimartín, Maria I, Haroun, Elisa, de la Torre, Maria V, Rojas, Antonia, Onieva, Montserrat L, Canto, Gabriela, Rodrigues, Alexandra, Forno, Andreia, Cabral, António J, Gonçalves, Rute, Vorozhko, Ilya, Sentsova, Tatyana, Chernyak, Olga, Denisova, Svetlana, Ilènko, Lidia, Muhortnich, Valery, Zimmermann, Caroline, Rohrbach, Alexander, Bakhsh, Faisal R, Boudewijn, Kollen, Oomkes-Pilon, Anne-Marie, Van Ginkle, Dorien, Šilar, Mira, Jeverica, Anja, Vesel, Tina, Avčin, Tadej, Korošec, Peter, van der Valk, Johanna, Berends, Irene, Arends, Nicolette, van Maaren, Maurits, Wichers, Harry, Emons, Joyce, Dubois, Anthony, de Jong, Nicolette, Matsyura, Oksana, Besh, Lesya, Huang, Chung-Hsiung, Jan, Tong-Rong, Stiefel, Gary, Tratt, Jean, Kirk, Kerrie, Carolino, Fabricia, Arasi, Stefania, Caminiti, Lucia, Crisafulli, Giuseppe, Fiamingo, Chiara, Fresta, Jlenia, Pajno, Giovanni, Remington, Ben, Kruizinga, Astrid, Marty Blom, W., Westerhout, Joost, Bijlsma, Sabina, Baumert, Joe, Blankestijn, Mark, Otten, Henny, Klemans, Rob, Michelsen-Huisman, Anouska D, van Os-Medendorp, Harmieke, Kruizinga, Astrid G, Versluis, Astrid, van Duijn, Gert, de Zeeuw-Brouwer, H. M, Castenmiller, Jacqueline J M, Noteborn, Hub P J M, Houben, Geert F, Bravin, Kristian, Luyt, David, Javed, Bushra, Couch, Phil, Munro, Christopher, Padfield, Phil, Sperrin, Matt, Byrne, Aideen, Oosthuizen, Lizalet, Kelleher, Carina, Ward, Fiona, Brosnan, Niamh, King, Graham, Corbet, Eva, Guzmán, Josué A H, García, Montserrat B, Asensio, Oscar, Navarrete, Laura V, Larramona, Helena, Miró, Xavier D, Pyrz, Katarzyna, Austin, Moira, Boloh, Yanne, Couch, Philip, Galloway, Deirdre, Hernandez, Pilar, Hourihane, Jonathan O, Kenna, Fiona, Majkowska-Wojciechowska, Barbara, Regent, Lynne, Themisb, Marina, Schnadt, Sabine, Semic-Jusufagic, Aida, Galvin, Audrey D, Kauppila, Tiina, Kuitunen, Mikael, Kitsioulis, Nikolaos A, Douladiris, Nikolaos, Kostoudi, Sofia, Manolaraki, Ioanna, Mitsias, Dimitris, Manousakis, Emmanouil, Papadopoulos, Nikolaos G, Knibb, Rebecca, Hammond, Jennifer, Cooke, Richard, Yrjänä, Jaakko, Hanni, Anna-Maija, Vähäsarja, Päivi, Mustonen, Oona, Dunder, Teija, Kulmala, Petri, Lasa, Eva, D’Amelio, Carmen, Martínez, Sara, Joral, Alejandro, Gastaminza, Gabriel, Goikoetxea, Maria J, Candy, David C A, Van Ampting, Marleen T J, Oude Nijhuis, Manon M, Butt, Assad M, Peroni, Diego G, Fox, Adam T, Knol, Jan, Michaelis, Louise J, Padua, Ines, Padrao, Patricia, Moreira, Pedro, Barros, Renata, Sharif, Hanan, Ahmed, Manzoor, Gomaa, Nehad, Mens, Joris, Smit, Koen, Timmermans, Frans, Poredoš, Tomaž, Jeverica, Anja K, Sedmak, Marjeta, Benedik, Evgen, Accetto, Meta, Zupančič, Mirjana, Yonamine, Glauce, Soldateli, Gustavo, Aquilante, Bruna, Pastorino, Antonio C, de Moraes Beck, Cleonir L, Gushken, Andrea K, de Barros Dorna, Mayra, dos Santos, Cristiane N, Castro, Ana P M, Al-Qahtani, Abdulhadi, Arnaout, Rand, Khaliq, Agha R, Amin, Rashid, Sheikh, Farrukh, Alvarez, Jorge, Anda, Marta, Palacios, Miriam, De Prada, Montserrat, Ponce, Carmen, Balbino, Bianca, Sibilano, Riccardo, Marichal, Thomas, Gaudenzio, Nicolas, Karasuyama, Hajime, Bruhns, Pierre, Tsai, Mindy, Reber, Laurent L, Galli, Stephen J, Ferreira, Ana R, Cernadas, Josefina R, del Campo García, Aida, Fernández, Sara P, Carrera, Nerea S, Sánchez-Cruz, Fernando B, Lorenzo, José R F, Claus, Stephanie, Pföhler, Claudia, Ruëff, Franziska, Treudler, Regina, Jaume, Mercedes E, Madroñero, Agustin, Perez, Maria T G, Julia, Juan C, Plovdiv, Charlotte H, Gethings, Lee, Langridge, Jim, Adel-Patient, Karine, Bernard, Hervé, Barcievic-Jones, Ivona, Sokolova, Raditsa, Yankova, Rumyana, Ivanovska, Mariya, Murdjeva, Marianna, Popova, Tatyana, Dermendzhiev, Svetlan, Karjalainen, Martin, Lehnigk, Ulrike, Brown, Duncan, Locklear, Julie C, Locklear, Julie, Maris, Ioana, Hourihane, Jonathan, Ornelas, Cristina, Caiado, Joana, Ferreira, Manuel B, Pereira-Barbosa, Manuel, Puente, Yolanda, Daza, Juan C, Monteseirin, Francisco J, Ukleja-Sokolowska, Natalia, Gawronska-Ukleja, Ewa, Zbikowska-Gotz, Magdalena, Bartuzi, Zbigniew, Sokolowski, Lukasz, Adams, Aine, Mahon, Bernard, English, Karen, Gourdon-Dubois, Nelly, Sellam, Laetitia, Pereira, Bruno, Michaud, Elodie, Messaoudi, Khaled, Evrard, Bertrand, Fauquert, Jean-Luc, Palomares, Francisca, Gomez, Gador, Rodriguez, Maria J, Galindo, Luisa, Molina, Ana, Paparo, Lorella, Mennini, Maurizio, Aitoro, Rosita, Wawrzeńczyk, Adam, Przybyszewski, Michał, Wawrzeńczyk, Anna, Sarıcoban, Hulya E, Ugras, Meltem, Yalvac, Zerrin, Flokstra-de Blok, Bertine M J, van der Velde, J. L, Vereda, Andrea, Ippolito, Clara, Traversa, Amaranta, Adriano, Daniela, Bianchi, Daniela M, Gallina, Silvia, Decastelli, Lucia, Makatsori, Melina, Miles, Anne, Devetak, Sonja P, Devetak, Iztok, Tabet, Soraya A, Trandbohus, Jeanette F, Winther, Pernille, Malling, Hans-Jørgen, Hansen, Kirsten S, Garvey, Lene H, Wang, Chia-Chi, Cheng, Yin-Hua, Tung, Chun-Wei, Dietrich, Mariola, Marenholz, Ingo, Kalb, Birgit, Grosche, Sarah, Blümchen, Katharina, Schlags, Rupert, Price, Mareike, Rietz, Sylke, Esparza-Gordillo, Jorge, Lau, Susanne, Lee, Young-Ae, Almontasheri, Ali, Bahkali, Mohammad A, Elshorbagi, Sahar, Alfhaid, Abdullah, Altamimi, Mashary, Madbouly, Eman, Al-Dhekri, Hassan, Arnaout, Rand K, Basagaña, Maria, Miquel, Sira, Bartolomé, Borja, Brix, Bettina, Rohwer, Stefanie, Brandhoff, Sandra, Berger, Alena, Suer, Waltraud, Weimann, Alf, Bueno, Cristina, Martín-Pedraza, Laura, Abián, Sara, Segundo-Acosta, Pablo S, López-Rodríguez, Juan C, Barderas, Rodrigo, Batanero, Eva, Cuesta-Herranz, Javier, Villalba, María T, Correia, Magna, Benito-Garcia, Filipe, Arêde, Cristina, Piedade, Susana, Morais-Almeida, Mário, Hindley, James, Yarham, Ross, Kuklinska-Pijanka, Anna, Gillick, David, Patient, Karine, Chapman, Martin D, Miranda, Ana, Matos, Eugénia, Sokolova, Anna, Rao, Huan, Baricevic-Jones, Ivona, Smith, Frances, Xue, Wentong, Magnusdottir, Helga, Vidarsdottir, Anna G, Lund, Sigrun, Jensen, Anders B, Ludviksson, Bjorn R, Simon, Reyna, Elfont, Robert, Bennett, Sean, Voyksner, Robert, de Lurdes Torre, Maria, Yürek, Songül, Faber, Margaretha A, Bastiaensen, Annick, Mangodt, Evelyne, van Gasse, Athina, Decuyper, Ine, Sabato, Vito, Hagendorens, Margo M, Bridts, Chris H, De Clerck, Luc S, Ebo, Didier, Schwarz, Susanne, Ziegert, Mandy, Albroscheit, Saskia, Schwager, Christian, Kull, Skadi, Behrends, Jochen, Röckendorf, Niels, Schocker, Frauke, Frey, Andreas, Homann, Arne, Becker, Wolf-Meinhard, Jappe, Uta, Zaabat, Nesrine, Osscini, Sylvia, Agabriel, Chantal, Sterling, Benoît, Carsin, Ania, Liabeuf, Valérie, Maćków, Monica, Zbróg, Alina, Bronkowska, Monica, Courtois, Justine, Gadisseur, Romy, Bertholet, Catherine, Lukas, Pierre, Cavalier, Etienne, Delahaut, Philippe, Quinting, Birgit, Gertmo, Margareta B, Hasseus, Ewa T, Barzylovych, Vladyslava, Oliveira, Júlio, Ensina, Luis F, Aranda, Carolina S, Dopazo, Leire, Lopez, Rebeca, Perez, Raquel, Santos-Diez, Laura, Bilbao, Agurtzane, Garcia, Juan M, Núñez, Ignacio G, Mármol, María Á A, Villarejo, María J B, Martos, José A B, Vergara, Marina S, García, José M I, Michalska, Agata, Sergiejko, Grzegorz, Zacniewski, Robert, Ghiordanescu, Ileana-Maria, Deaconu, Cristina, Popescu, Mihaela, Bumbacea, Roxana S, Ibranji, Alkerta, Nikolla, Elida, Loloci, Gjustina, Juel-Berg, Nanna, Larsen, Lau F, Poulsen, Lars K, Marcelino, João, Prata, Ricardo, Costa, Ana C, Duarte, Fátima, Neto, Marta, Santos, Jennifer, Pestana, Luís C, Sampaio, Daniel, Minale, Paola, Dignetti, Paola, Bignardi, Donatella, Nedelea, Irena, Popescu, Florin-Dan, Vieru, Mariana, Secureanu, Florin-Adrian, Ganea, Carmen S, Vieira, Miguel, Silva, José P M, Watts, Timothy, Watts, Sophia, Lomikovska, Marta, Peredelskaya, Marina, Nenasheva, Natalia, Filipovic, Ivana, Zivkovic, Zorica, Filipovic, Djordje, Higgs, Jennette, Warner, Amena, and Jones, Carla

Published
2017

29. Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

Author

Afd Pharmacology, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-1, van Bilsen, Jolanda H M, Sienkiewicz-Szłapka, Edyta, Lozano-Ojalvo, Daniel, Willemsen, Linette E. M., Antunes, Celia M, Molina, Elena, Smit, Joost J., Wróblewska, Barbara, Wichers, Harry J., Knol, Edward F., Ladics, Gregory S, Pieters, Raymond H. H., Denery-Papini, Sandra, Vissers, Yvonne M, Bavaro, Simona L, Larré, Colette, Verhoeckx, Kitty C M, Roggen, Erwin L, Afd Pharmacology, Sub IRAS Tox ITX (immunotoxicologie), dIRAS RA-1, van Bilsen, Jolanda H M, Sienkiewicz-Szłapka, Edyta, Lozano-Ojalvo, Daniel, Willemsen, Linette E. M., Antunes, Celia M, Molina, Elena, Smit, Joost J., Wróblewska, Barbara, Wichers, Harry J., Knol, Edward F., Ladics, Gregory S, Pieters, Raymond H. H., Denery-Papini, Sandra, Vissers, Yvonne M, Bavaro, Simona L, Larré, Colette, Verhoeckx, Kitty C M, and Roggen, Erwin L

Published
2017

30. Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

Author

MS Dermatologie/Allergologie, CDL Celdiagnostiek, Infection & Immunity, CTI, van Bilsen, Jolanda H M, Sienkiewicz-Szłapka, Edyta, Lozano-Ojalvo, Daniel, Willemsen, Linette E M, Antunes, Celia M, Molina, Elena, Smit, Joost J, Wróblewska, Barbara, Wichers, Harry J, Knol, Edward F, Ladics, Gregory S, Pieters, Raymond H H, Denery-Papini, Sandra, Vissers, Yvonne M, Bavaro, Simona L, Larré, Colette, Verhoeckx, Kitty C M, Roggen, Erwin L, MS Dermatologie/Allergologie, CDL Celdiagnostiek, Infection & Immunity, CTI, van Bilsen, Jolanda H M, Sienkiewicz-Szłapka, Edyta, Lozano-Ojalvo, Daniel, Willemsen, Linette E M, Antunes, Celia M, Molina, Elena, Smit, Joost J, Wróblewska, Barbara, Wichers, Harry J, Knol, Edward F, Ladics, Gregory S, Pieters, Raymond H H, Denery-Papini, Sandra, Vissers, Yvonne M, Bavaro, Simona L, Larré, Colette, Verhoeckx, Kitty C M, and Roggen, Erwin L

Published
2017

31. Application of the adverse outcome pathway (AOP) concept to structure the available in vivo and in vitro mechanistic data for allergic sensitization to food proteins

Author

Van Bilsen, Jolanda H.M., Sienkiewicz-Szłapka, Edyta, Lozano-Ojalvo, Daniel, Willemsen, Linette E.M., Antunes, Celia M., Molina, Elena, Smit, Joost J., Wróblewska, Barbara, Wichers, Harry J., Knol, Edward F., Ladics, Gregory S., Pieters, Raymond H.H., Denery-Papini, Sandra, Vissers, Yvonne M., Bavaro, Simona L., Larré, Colette, Verhoeckx, Kitty C.M., Roggen, Erwin L., Van Bilsen, Jolanda H.M., Sienkiewicz-Szłapka, Edyta, Lozano-Ojalvo, Daniel, Willemsen, Linette E.M., Antunes, Celia M., Molina, Elena, Smit, Joost J., Wróblewska, Barbara, Wichers, Harry J., Knol, Edward F., Ladics, Gregory S., Pieters, Raymond H.H., Denery-Papini, Sandra, Vissers, Yvonne M., Bavaro, Simona L., Larré, Colette, Verhoeckx, Kitty C.M., and Roggen, Erwin L.

Abstract

Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. This constitutes a potential public health problem and a challenge to risk assessors and managers as the existing understanding of the pathophysiological processes and the currently available biological tools for prediction of the risk for food allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo and in vitro data describing molecular and cellular events potentially involved in food sensitization. However, these events have not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challenge current hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understanding of sensitization induction to food proteins by applying the concept of adverse outcome pathway (AOP). Main body: The proposed AOP for food sensitization is based on information on molecular and cellular mechanisms and pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemical skin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratory sensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell-cell interactions and tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use in testing and assessment of proteins for their sensitizing potential. Conclusion: The application of the AOP concept to structure mechanistic in vivo and in vitro knowledge has made it possible to identify a number of methods, each addressing a specific KE, that provide information about the food allergenic potential of new proteins. When applied in the context of an integrated strategy these methods may reduce, if not replace, current animal testing approaches. The proposed AOP will

Published
2017

32. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Author

Bøgh, Katrine Lindholm, van Bilsen, Jolanda, Głogowski, Robert, López-Expósito, Iván, Bouchaud, Grégory, Blanchard, Carine, Bodinier, Marie, Smit, Joost, Pieters, Raymond, Bastiaan-Net, Shanna, de Wit, Nicole, Untersmayr, Eva, Adel-Patient, Karine, Knippels, Leon, Epstein, Michelle M, Noti, Mario, Nygaard, Unni Cecilie, Kimber, Ian, Verhoeckx, Kitty, O'Mahony, Liam, Sub IRAS Tox ITX (immunotoxicologie), Sub General Pharmacology, dIRAS RA-1, Pharmacology, National Food Institute, Technical University of Denmark [Lyngby] (DTU), TNO, Warsaw University of Life Sciences (SGGW), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Unité de recherche sur les Biopolymères, Interactions Assemblages (BIA), Institut National de la Recherche Agronomique (INRA), Nestlé, Institute for Risk Assessment Sciences, Utrecht University [Utrecht], Wageningen University and Research Centre (WUR), Department of Pathophysiology and Allergy Research, Medizinische Universität Wien = Medical University of Vienna-Christian Doppler Laboratory for Immunomodulation, Service de Pharmacologie et d'Immunoanalyse (SPI), Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris Saclay (COmUE), Danone Research, Utrecht Institute for Pharmaceutical Sciences (UIPS), Medizinische Universität Wien = Medical University of Vienna, University of Bern, Norwegian institute for public health, University of Manchester [Manchester], Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), EU, European Cooperation in Science and Technology, Swiss National Science Foundation, European Commission, Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Nestlé S.A., Service de Pharmacologie et Immunoanalyse (SPI), Médicaments et Technologies pour la Santé (MTS), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Sub IRAS Tox ITX (immunotoxicologie), Sub General Pharmacology, dIRAS RA-1, and Pharmacology

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Emerging technologies, [SDV]Life Sciences [q-bio], Immunology, Population, RAPID - Risk Analysis for Products in Development, Novel food, Review, Biology, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Life, Food allergy, [SDV.IDA]Life Sciences [q-bio]/Food engineering, medicine, Immunology and Allergy, Food and Nutrition, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Food allergens, education, VLAG, Food, Health & Consumer Research, 2. Zero hunger, education.field_of_study, business.industry, animal models, food allergy, hazard identification, novel allergens, medicine.disease, Test protein, 3. Good health, Biotechnology, Animal models, 030104 developmental biology, Health & Consumer Research, Hazard identification, Agriculture, Food, Identification (biology), ELSS - Earth, Life and Social Sciences, business, Novel allergens, Healthy Living
Abstract

Bøgh et al., Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured., The authors are all part of the COST Action FA1402 entitled: Improving Allergy Risk Assessment Strategy for New Food Proteins (ImpARAS). LOM is supported by Swiss National Foundation grants (Project Numbers: CRSII3_154488 and 310030-144219) and European Union research grants.

Published
2016

33. Primary respiratory and food allergy to mealworm

Author

Broekman, Henrike C.H.P., primary, Knulst, André C., additional, den Hartog Jager, Constance F., additional, van Bilsen, Jolanda H.M., additional, Raymakers, Florine M.L., additional, Kruizinga, Astrid G., additional, Gaspari, Marco, additional, Gabriele, Caterine, additional, Bruijnzeel-Koomen, Carla A.F.M., additional, Houben, Geert F., additional, and Verhoeckx, Kitty C.M., additional

Published
2017
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34. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models

Author

Sub IRAS Tox ITX (immunotoxicologie), Sub General Pharmacology, dIRAS RA-1, Pharmacology, Bøgh, Katrine Lindholm, van Bilsen, Jolanda, Głogowski, Robert, López-Expósito, Iván, Bouchaud, Grégory, Blanchard, Carine, Bodinier, Marie, Smit, Joost, Pieters, Raymond, Bastiaan-Net, Shanna, de Wit, Nicole, Untersmayr, Eva, Adel-Patient, Karine, Knippels, Leon, Epstein, Michelle M, Noti, Mario, Nygaard, Unni Cecilie, Kimber, Ian, Verhoeckx, Kitty, O'Mahony, Liam, Sub IRAS Tox ITX (immunotoxicologie), Sub General Pharmacology, dIRAS RA-1, Pharmacology, Bøgh, Katrine Lindholm, van Bilsen, Jolanda, Głogowski, Robert, López-Expósito, Iván, Bouchaud, Grégory, Blanchard, Carine, Bodinier, Marie, Smit, Joost, Pieters, Raymond, Bastiaan-Net, Shanna, de Wit, Nicole, Untersmayr, Eva, Adel-Patient, Karine, Knippels, Leon, Epstein, Michelle M, Noti, Mario, Nygaard, Unni Cecilie, Kimber, Ian, Verhoeckx, Kitty, and O'Mahony, Liam

Published
2016

35. Evaluation of the sensitizing potential of food proteins using two mouse models

Author

Sub IRAS Tox ITX (immunotoxicologie), Sub Immunopharmacology, dIRAS RA-1, Smit, Joost, Zeeuw-Brouwer, Mary-Lène de, van Roest, Manon, de Jong, Govardus, van Bilsen, Jolanda, Sub IRAS Tox ITX (immunotoxicologie), Sub Immunopharmacology, dIRAS RA-1, Smit, Joost, Zeeuw-Brouwer, Mary-Lène de, van Roest, Manon, de Jong, Govardus, and van Bilsen, Jolanda

Published
2016

36. Modifying the infant's diet to prevent food allergy

Author

Grimshaw, Kate, primary, Logan, Kirsty, additional, O'Donovan, Sinead, additional, Kiely, Mairead, additional, Patient, Karine, additional, van Bilsen, Jolanda, additional, Beyer, Kirsten, additional, Campbell, Dianne E, additional, Garcia-Larsen, Vanessa, additional, Grabenhenrich, Linus, additional, Lack, Gideon, additional, Mills, Clare, additional, Wal, Jean-Michel, additional, and Roberts, Graham, additional

Published
2016
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40. Current challenges facing the assessment of the allergenic capacity of food allergens in animal models.

Author

Lindholm Bøgh, Katrine, van Bilsen, Jolanda, Głogowski, Robert, López-Expósito, Iván, Bouchaud, Grégory, Blanchard, Carine, Bodinier, Marie, Smit, Joost, Pieters, Raymond, Bastiaan-Net, Shanna, de Wit, Nicole, Untersmayr, Eva, Adel-Patient, Karine, Knippels, Leon, Epstein, Michelle M., Noti, Mario, Nygaard, Unni Cecilie, Kimber, Ian, Verhoeckx, Kitty, and O'Mahony, Liam

Subjects
*FOOD allergy, *ALLERGENS, *FOOD safety
Abstract

Food allergy is a major health problem of increasing concern. The insufficiency of protein sources for human nutrition in a world with a growing population is also a significant problem. The introduction of new protein sources into the diet, such as newly developed innovative foods or foods produced using new technologies and production processes, insects, algae, duckweed, or agricultural products from third countries, creates the opportunity for development of new food allergies, and this in turn has driven the need to develop test methods capable of characterizing the allergenic potential of novel food proteins. There is no doubt that robust and reliable animal models for the identification and characterization of food allergens would be valuable tools for safety assessment. However, although various animal models have been proposed for this purpose, to date, none have been formally validated as predictive and none are currently suitable to test the allergenic potential of new foods. Here, the design of various animal models are reviewed, including among others considerations of species and strain, diet, route of administration, dose and formulation of the test protein, relevant controls and endpoints measured. [ABSTRACT FROM AUTHOR]

Published
2016
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42. Identification of Genetic Loci in Lactobacillus plantarum That Modulate the Immune Response of Dendritic Cells Using Comparative Genome Hybridization

Author

Meijerink, Marjolein, primary, van Hemert, Saskia, additional, Taverne, Nico, additional, Wels, Michiel, additional, de Vos, Paul, additional, Bron, Peter A., additional, Savelkoul, Huub F., additional, van Bilsen, Jolanda, additional, Kleerebezem, Michiel, additional, and Wells, Jerry M., additional

Published
2010
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46. Bovine spermatozoa: An in vitro model for reproductive toxicity?

Author

Tegelenbosch-Schouten, Mariska M., primary, Arabi, Sabina, additional, Balduzzi, Donatella, additional, van Bilsen, Jolanda H.M., additional, Brouwer, Mary-Lène H.M.H., additional, Dijkstra, Anja, additional, Galli, Andrea, additional, van der Horst-Groeneveld, Linda J.M.L., additional, Theunissen, Peter T., additional, Wolterbeek, André P.M., additional, and Waalkens-Berendsen, Ine D., additional

Published
2006
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47. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans

Author

Morgan, Mary E., primary, van Bilsen, Jolanda H.M., additional, Bakker, Aleida M., additional, Heemskerk, Bianca, additional, Schilham, Marco W., additional, Hartgers, Franca C., additional, Elferink, Berendina G., additional, van der Zanden, Linda, additional, de Vries, René R.P., additional, Huizinga, Tom W.J., additional, Ottenhoff, Tom H.M., additional, and Toes, René E.M., additional

Published
2005
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50. Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans

Author

Morgan, Mary E., van Bilsen, Jolanda H.M., Bakker, Aleida M., Heemskerk, Bianca, Schilham, Marco W., Hartgers, Franca C., Elferink, Berendina G., van der Zanden, Linda, de Vries, René R.P., Huizinga, Tom W.J., Ottenhoff, Tom H.M., and Toes, René E.M.

Subjects
*MESSENGER RNA, *ANTIGENS, *T cells, *TRANSCRIPTION factors
Abstract

Abstract: Expression of the transcription factor Foxp3 (forkhead box P3) has been implicated as a key element for CD25+ T regulatory cell function in mice. However, literature over similar involvement of FOXP3 expression in human T regulatory cells is limited. We found that, unlike murine cells, FOXP3 mRNA expression could be induced in human CD25− and CD8+ peripheral blood mononuclear cells, which were both negative for FOXP3 mRNA expression after isolation. Expression of FOXP3 mRNA began as soon as 24–40 hours after stimulation, demonstrating a correlation between activation and FOXP3 mRNA expression in human cells. In order to determine whether FOXP3 expression is confined to CD4+CD25+ T cells with a regulatory phenotype, we analyzed several well-defined T-cell clones and lines with various specificities. Surprisingly, expression of FOXP3 mRNA was detected in all clones and limited to the CD25hi populations. Nonetheless, the CD25hi fraction did not display regulatory properties because both the CD25hi and CD25low populations exhibited a similar proliferative- and interferon-γ–secreting potential after antigenic stimulation. These results indicate that FOXP3 expression in humans, unlike mice, may not be specific for cells with a regulatory phenotype and may be only a consequence of activation status. [Copyright &y& Elsevier]

Published
2005
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