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.
Primary respiratory and food allergy to mealworm Broekman, Henrike C.H.P., MD; Knulst, André C., MD, PhD; den Hartog Jager, Constance F., BSc ...
Journal of allergy and clinical immunology,
08/2017, Letnik:
140, Številka:
2
Journal Article
Recenzirano
Sensitization profiles (specific IgE sIgE, immunoblot, and the basophil activation test BAT), allergens involved (liquid chromatography-mass spectrometry) and the development of clinical allergy to ...shrimp (open food challenge) and mealworm (double-blind, placebo-controlled food challenger DBPCFC) were investigated (for details, see the Methods section in this article's Online Repository at www.jacionline.org). All subjects had a negative oral food challenge result for shrimp, and only subject 3 and 4 had positive DBPCFC results for mealworm. Because 3 of our subjects had higher sIgE levels to mealworm than to any other food or inhalant allergen, mealworm might be the primary sensitizer. Furthermore, immunoblots from patients with shrimp allergy1 showed different binding patterns compared with those from the 4 primary patients with mealworm allergy, and their basophil activation to mealworm was stronger than for shrimp (see Fig E1 in this article's Online Repository at www.jacionline.org). Because levels of sIgE to shrimp and HDM were low, inhibition studies were not feasible. ...mealworm exposure can lead Tropomyosin-like(Tribolium castaneum) D6X4X3 85 38 12 23 32.3 Actin-87E (Drosophila melanogaster) P10981 60 22 9 14 41.8 TM-E1A = cuticular protein (Tenebrio molitor) Q9TXE4 32 27 3 9 23.2 Other known allergens identified Chitin-binding protein(Nasonia vitripennis) K7IX02 29 8 4 7 23.0 Myosin heavy-like(Tribolium castaneum) D6WVJ3 27 15 9 10 262.1 Troponin T-like(Tribolium castaneum) D6W953 17 14 5 6 45.7 Myosin light chain 2(Tribolium castaneum) D6WZU7 12 9 3 4 31.3 Arginine kinase (fragmentLasippa tiga) D1L9H9 11 19 2 2 12.0 Table E3IgE-binding proteins identified in 4 human subjectsProteins were...
Oral immunotherapy (OIT) is a promising therapeutic approach to treat food allergic patients. However, concerns with regards to safety and long-term efficacy of OIT remain. There is a need to ...identify biomarkers that predict, monitor and/or evaluate the effects of OIT. Here we present a method to select candidate biomarkers for efficacy and safety assessment of OIT using the computational approaches Bayesian networks (BN) and Topological Data Analysis (TDA).
Data were used from fructo-oligosaccharide diet-supported OIT experiments performed in 3 independent cow's milk allergy (CMA) and 2 independent peanut allergy (PNA) experiments in mice. Bioinformatical approaches were used to understand the data structure. The BN predicted the efficacy of OIT in the CMA with 86% and indicated a clear effect of scFOS/lcFOS on allergy parameters. For the PNA model, this BN (trained on CMA data) predicted an efficacy of OIT with 76% accuracy and shows similar effects of the allergen, treatment and diet as compared to the CMA model. The TDA identified clusters of biomarkers closely linked to biologically relevant clinical symptoms and also unrelated and redundant parameters within the network.
Here we provide a promising application of computational approaches to a) compare mechanistic features of two different food allergies during OIT b) determine the biological relevance of candidate biomarkers c) generate new hypotheses to explain why CMA has a different disease pattern than PNA and d) select relevant biomarkers for future studies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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 AOP for food sensitization helps to implement in vitro testing approaches.•Innate immune mechanisms are easier to address than adaptive response.•No in vitro protocols have been established for investigating IgE-class switching.•Ex vivo strategies are promising to address multiple key events at the same assay.
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.
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,
, and other immune activation regulators (e.g.,
), but also identified less obvious candidates (e.g.,
). Comparison of the different early life periods resulted in the prediction of 11 key early life genes overlapping all early life periods (
, and
, 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.
Metabolic disorders, such as obesity and type 2 diabetes have a large impact on global health, especially in industrialized countries. Tissue-specific chronic low-grade inflammation is a key ...contributor to complications in metabolic disorders. To support therapeutic approaches to these complications, it is crucial to gain a deeper understanding of the inflammatory dynamics and to monitor them on the individual level. To this end, blood-based biomarkers reflecting the tissue-specific inflammatory dynamics would be of great value. Here, we describe an
in silico
approach to select candidate biomarkers for tissue-specific inflammation by using
a priori
mechanistic knowledge from pathways and tissue-derived molecules. The workflow resulted in a list of candidate markers, in part consisting of literature confirmed biomarkers as well as a set of novel, more innovative biomarkers that reflect inflammation in the liver and adipose tissue. The first step of biomarker verification was on murine tissue gene-level by inducing hepatic inflammation and adipose tissue inflammation through a high-fat diet. Our data showed that
in silico
predicted hepatic markers had a strong correlation to hepatic inflammation in the absence of a relation to adipose tissue inflammation, while others had a strong correlation to adipose tissue inflammation in the absence of a relation to liver inflammation. Secondly, we evaluated the human translational value by performing a curation step in the literature using studies that describe the regulation of the markers in human, which identified 9 hepatic (such as Serum Amyloid A, Haptoglobin, and Interleukin 18 Binding Protein) and 2 adipose (Resistin and MMP-9) inflammatory biomarkers at the highest level of confirmation. Here, we identified and pre-clinically verified a set of
in silico
predicted biomarkers for liver and adipose tissue inflammation which can be of great value to study future development of therapeutic/lifestyle interventions to combat metabolic inflammatory complications.
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.
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.
Recommendations and guidelines on the prevention of food allergy have changed in recent decades. The aim of this review of the current evidence and ongoing studies is to provide a comprehensive and ...up to date picture of prevention of food allergy for healthcare professionals. The review was undertaken as part of the European Union funded Integrated Approaches to Food Allergy and Allergen Management (iFAAM) study. This is a wide ranging project bringing together expertise across the breadth of food allergy research. Specifically, the review discusses dietary manipulation in food allergy prevention, and covers the possible preventive strategies of allergen avoidance, early allergen introduction, general nutrition and supplements, as well as other strategies, such as prebiotics and probiotics. The review concludes that despite agreement that allergen avoidance strategies should not be undertaken for allergy prevention, there is currently no consensus regarding what actions should be recommended beyond exclusive breastfeeding for the first 4–6 months of life. Recent and upcoming trial results, which are detailed in this review, should help inform the debate and add clarity to the topic.
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