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

Background: The introduction of whole new foods in a population may lead to sensitization and food allergy. Thisconstitutes a potential public health problem and a challenge to risk assessors and managers as the existing understandingof the pathophysiological processes and the currently available biological tools for prediction of the risk forfood allergy development and the severity of the reaction are not sufficient. There is a substantial body of in vivo andin vitro data describing molecular and cellular events potentially involved in food sensitization. However, these eventshave not been organized in a sequence of related events that is plausible to result in sensitization, and useful to challengecurrent hypotheses. The aim of this manuscript was to collect and structure the current mechanistic understandingof 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 mechanismsand pathways evidenced to be involved in sensitization by food and food proteins and uses the AOPs for chemicalskin sensitization and respiratory sensitization induction as templates. Available mechanistic data on protein respiratorysensitization were included to fill out gaps in the understanding of how proteins may affect cells, cell–cell interactionsand tissue homeostasis. Analysis revealed several key events (KE) and biomarkers that may have potential use intesting 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 madeit possible to identify a number of methods, each addressing a specific KE, that provide information about the foodallergenic potential of new proteins. When applied in the context of an integrated strategy these methods mayreduce, if not replace, current animal testing approaches. The proposed AOP will be shared at the www.aopwiki.orgplatform 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.