New publications in the field of food allergy (co-)authored by the TNO Food Allergy and Immune Health Modeling team

In the first paper we summarize the evidence of successful application of metabolic challenge tests in type 2 diabetes, metabolic syndrome, obesity, and unhealthy ageing. Moreover, we elaborate on future strategies to (re)gain inflammatory flexibility by ‘training’ the inflammatory response by regular mild and metabolic triggers.

Willem van den Brink, Jolanda van Bilsen, Kanita Salic, Femke Hoevenaars, Lars Verschuren, Robert Kleemann, Jildau Bouwman, Gabriele Ronnett, Ben van Ommen, Suzan Wopereis.
Current and future nutritional strategies to modulate inflammatory dynamics in metabolic disorders.  Front. Nutr., 26 August 2019. doi: 10.3389/fnut.2019.00129.

Also a review was published which focuses on the different mechanisms via which the pre- and probiotics exert their beneficial effects on the host, addressing their immunomodulatory properties in particular.

Peters VBM, van de Steeg E, van Bilsen J, Meijerink M. Mechanisms and immunomodulatory properties of pre- and probiotics.  Benef Microbes. 2019 Mar 4:1-12. doi: 10.3920/BM2018.0066.

A comprehensive overview is provided 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.

Castan L, Bøgh KL, Maryniak NZ, Epstein MM, Kazemi S, O’Mahony L, Bodinier M, Smit J, van Bilsen J, Blanchard C, Głogowski R, Kozáková H, Schwarzer M, Noti M, de Wit N, Bouchaud G, Bastiaan-Net S.  Overview of in vivo and ex vivo endpoints in murine food allergy models: Suitable for evaluation of the sensitizing capacity of novel proteins? Allergy . 2019 Jun 12. doi: 10.1111/all.13943.


Several papers were published describing new insights in the field of protein allergenicity assessment.

In a 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.

Lozano-Ojalvo D, Benedé S, Antunes CL, Bavaro SL, Bouchaud G, Costa A, Denery S, Diaz-Perles A, Garrido-Arandia M, Gavrovic-Jankulovic M, Hayen s, Martinez M, Molina E, Monaci L, Pieters R, Villemin C, Wiggers H, Wróblewska B, Willemsen L, Roggen E, van Bilsen J. Applying the adverse outcome pathway (AOP) for food sensitization to support in vitro testing strategies. Trends in Food Science & Technology 85 (2019) 307–319. doi:10.1016/j.tifs.2019.01.014.

We also published a paper describing the development of an artificial intelligence-based allergenicity prediction model for novel proteins.

Westerhout J, Houben GG, Verhoeckx KC, Krone T, Snippe A, Babé L, McClain SU, Ladics GS. Allergenicity prediction of novel and modified proteins: Not a mission impossible! Development of a Random Forest allergenicity prediction model. Regul Toxicol Pharmacol. 2019 Jul 13:104422. doi: 10.1016/j.yrtph.2019.104422.

TNO also contributed to an EAACI position paper comparing insect hypersensitivity induced by bite, sting, inhalation or ingestion in human beings and animals.

Pali-Schöll I, Blank S, Verhoeckx K, Mueller RS, Janda J, Marti E, Seida AA, Rhyner C, DeBoer DJ, Jensen-Jarolim E. EAACI position paper: Comparing insect hypersensitivity induced by bite, sting, inhalation or ingestion in human beings and animals. Allergy. 2019 May;74(5):874-887. doi: 10.1111/all.13722. Epub 2019 Feb 6.


In the next paper, we propose that the strategy for allergenicity risk assessment of new or modified food proteins and the methodologies applied should be governed by the risk management questions to be answered, reflected in the information needed by risk managers to enable their informed decision making.

Houben G, Blom M, Alvito P, Assunção R, Crevel R, Fæste CK, Le TM, Madsen CB, Remington B, Stroheker T, Vassilopoulou E, Verhoeckx K, Žiarovská J, Constable A. Defining the targets for the assessment of IgE-mediated allergenicity of new or modified food proteins. Food Chem Toxicol. 2019 May;127:61-69. doi: 10.1016/j.fct.2019.02.036.


Two published papers focus on different aspects of oral immune therapy.


A study by Remington et al. quantifies the relative risk reduction in a double-blind, placebo-controlled Phase 3 study population of children treated with EPIT for 12 months with either a peanut patch or a placebo patch.

Remington BC, Krone T, Kim EH, Bird JA, Green TD, Lack G, Fleischer DM, Koppelman SJ. Estimated Risk Reduction to Packaged Food Reactions by Epicutaneous Immunotherapy (EPIT) for Peanut Allergy. Annals of Allergy, Asthma and Immunology (2019). doi:

The following publication describes a method to select candidate biomarkers for efficacy and safety assessment of oral immune therapy using the computational approaches Bayesian networks (BN) and Topological Data Analysis (TDA).

Van Bilsen JHM, Verschuren L, Wagenaar L, Vonk MM, van Esch BCAM, Knippels LMJ, Garssen J, Smit JJ, Pieters RHH and van den Broek T. A network-based approach for identifying suitable biomarkers for oral immunotherapy of food allergy. BMC Bioinformatics. 2019 Apr 23;20(1):206. doi: 10.1186/s12859-019-2802-9.


Finally three paper were focusing on risk assessment and risk management of food allergens.


The first paper resulted from the EU project Integrated Approaches to Food Allergen and Allergy Risk Management (iFAAM) in which TNO participated. This project aimed to improve the management of food allergens by the food industry for the benefit of people with food allergies. Within iFAAM, a clinically validated tiered risk assessment approach for food allergens was developed. Two cross-stakeholder iFAAM workshops were held on 13-14 December 2016 and 19-20 April 2018. The paper describes the outcomes from these workshops. This provides the basis for the development of more informative and transparent labelling that will ultimately improve management and well-being in consumers with food allergy.

DunnGalvin A, Roberts G, Schnadt S, Astley S, Austin M, Blom WM, Baumert J, Chan CH, Crevel RWR, Grimshaw KEC, Kruizinga AG, Regent L, Taylor S, Walker M, Mills C. Evidence based approaches to the application of Precautionary Allergen Labelling: Report from two iFAAM workshops. Clin Exp Allergy. 2019 Sep;49(9):1191-1200 .

In an effort to standardize individual food challenge data reporting and reduce variability in subsequent population dose distribution results, Westerhout and an international clinical author group have published a framework that guides food challenge data interpretation with over 90 examples and different scenarios for determining individual allergic thresholds. The framework provides a transparent, flexible template for interpretation of food challenge results. It provides a step forward towards harmonized food allergy risk assessment & risk management and the framework can be updated in the future based on potential changes in stakeholder opinions / requirements. This publication is selected as Editors’ Choice for the November issue of JACI and will be highlighted on the American Academy of Allergy Asthma & Immunology (AAAAI) website.

Westerhout J, Baumert JL, Blom WM, Allen KJ, Ballmer-Weber B, Crevel RWR, Dubois AEJ, Fernández-Rivas M, Greenhawt MJ, Hourihane JO, Koplin JJ, Kruizinga AG, Le TM, Sampson HA, Shreffler WG, Turner PJ, Taylor SL, Houben GF, Remington BC. Deriving individual threshold doses from clinical food challenge data for population risk assessment of food allergens. J Allergy Clin Immunol. 2019 Aug 22. pii: S0091-6749(19)31093-0.

The following paper describes the analysis that was performed to establish the optimal food consumption estimate for a deterministic food allergy risk assessment. With this, assessors have a guide on what food consumption data to use when assessing the risk from unintended allergen presence in food products. The P75 is the optimal point estimate for use, because it meets the safety objective and is adequately conservative for a public health context.

Blom WM, Remington BC, Baumert JL, Bucchini L, Crépet A, Crevel RWR, Madsen CB, Taylor SL, Houben GF, Kruizinga AG. Sensitivity analysis to derive a food consumption point estimate for deterministic food allergy risk assessment. Food Chem Toxicol. 2019 Mar;125:413-421. doi: 10.1016/j.fct.2019.01.025.