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Receptor Mediated Effects of Advanced Glycation End Products (AGEs) on Innate and Adaptative Immunity: Relevance for Food Allergy.
Briceno Noriega, D, Zenker, HE, Croes, CA, Ewaz, A, Ruinemans-Koerts, J, Savelkoul, HFJ, van Neerven, RJJ, Teodorowicz, M
Nutrients. 2022;(2)
Abstract
As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.
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Mechanisms Underlying the Skin-Gut Cross Talk in the Development of IgE-Mediated Food Allergy.
van Splunter, M, Liu, L, van Neerven, RJJ, Wichers, HJ, Hettinga, KA, de Jong, NW
Nutrients. 2020;(12)
Abstract
Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children.
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Epithelial-stromal crosstalk and fibrosis in eosinophilic esophagitis.
Muir, AB, Wang, JX, Nakagawa, H
Journal of gastroenterology. 2019;(1):10-18
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Abstract
Eosinophilic esophagitis (EoE) is a food allergen-induced inflammatory disorder. EoE is increasingly recognized as a cause of swallowing dysfunction, food impaction and esophageal stricture. Inflammation of the esophageal mucosa involves immune cell infiltrate, reactive epithelial changes and fibroblast activation, culminating in robust tissue remodeling toward esophageal fibrosis characterized by excess collagen deposition in the subepithelial lamina propria. Fibrosis contributes to a unique mechanical property of the EoE-affected esophagus that is substantially stiffer than the normal esophagus. There is a great need to better understand the processes behind esophageal fibrosis in order to foster improved diagnostic tools and novel therapeutics for EoE-related esophageal fibrosis. In this review, we discuss the role of esophageal inflammatory microenvironment that promotes esophageal fibrosis, with specific emphasis upon cytokines-mediated functional epithelial-stromal interplays, recruitment and activation of a variety of effector cells, and tissue stiffness. We then explore the current state of clinical methodologies to detect and treat the EoE-related esophageal stricture.
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Personalized Nutrition Approach in Food Allergy: Is It Prime Time Yet?
D'Auria, E, Abrahams, M, Zuccotti, GV, Venter, C
Nutrients. 2019;(2)
Abstract
The prevalence of food allergy appears to be steadily increasing in infants and young children. One of the major challenges of modern clinical nutrition is the implementation of individualized nutritional recommendations. The management of food allergy (FA) has seen major changes in recent years. While strict allergen avoidance is still the key treatment principle, it is increasingly clear that the avoidance diet should be tailored according to the patient FA phenotype. Furthermore, new insights into the gut microbiome and immune system explain the rising interest in tolerance induction and immunomodulation by microbiota-targeted dietary intervention. This review article focuses on the nutritional management of IgE mediated food allergy, mainly focusing on different aspects of the avoidance diet. A personalized approach to managing the food allergic individual is becoming more feasible as we are learning more about diagnostic modalities and allergic phenotypes. However, some unmet needs should be addressed to fully attain this goal.
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Food Allergies: Current and Future Treatments.
Licari, A, Manti, S, Marseglia, A, Brambilla, I, Votto, M, Castagnoli, R, Leonardi, S, Marseglia, GL
Medicina (Kaunas, Lithuania). 2019;(5)
Abstract
Food allergies are an increasingly public health problem, affecting up to 10% of children and causing a significant burden on affected patients, resulting in dietary restrictions, fear of accidental ingestion and related risk of severe reactions, as well as a reduced quality of life. Currently, there is no specific cure for a food allergy, so the only available management is limited to strict dietary avoidance, education on prompt recognition of symptoms, and emergency treatment of adverse reactions. Several allergen specific- and nonspecific-therapies, aiming to acquire a persistent food tolerance, are under investigation as potential treatments; however, to date, only immunotherapy has been identified as the most promising therapeutic approach for food allergy treatment. The aim of this review is to provide an updated overview on changes in the treatment landscape for food allergies.
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Feeding difficulties in children with non-IgE-mediated food allergic gastrointestinal disorders.
Chehade, M, Meyer, R, Beauregard, A
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2019;(6):603-609
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Abstract
OBJECTIVE To review the signs and symptoms of feeding difficulties in children with non-IgE-mediated food allergic gastrointestinal disorders and provide practical advice, with the goal of guiding the practitioner to timely referral for further evaluation and therapy. Various management approaches are also discussed. DATA SOURCES Articles and chapters related to normal feeding patterns and the diagnosis and management of feeding difficulties in children were reviewed. STUDY SELECTIONS Selections were based on relevance to the topic and inclusion of diagnostic and management recommendations. RESULTS Because most non-IgE-mediated food allergic gastrointestinal disorders occur in early childhood, feeding skills can be disrupted. Feeding difficulties can result in nutritional deficiencies, faltering growth, and a significant impact on quality of life. Specific symptoms related to each non-IgE-mediated food allergic gastrointestinal disorder can lead to distinctive presentations, which should be differentiated from simple picky eating. Successful management of feeding difficulties requires that the health care team views the problem as a relational disorder between the child and the caregiver and views its association with the symptoms experienced as a result of the non-IgE-mediated food allergic gastrointestinal disorder. Addressing the child's concern with eating needs to be done in the context of the family unit, with coaching provided to the caregiver as necessary while ensuring nutritional adequacy. Treatment approaches, including division of responsibility, food chaining, and sequential oral sensory, are commonly described in the context of feeding difficulties. CONCLUSION A multidisciplinary approach to management of feeding difficulties in non-IgE-mediated food allergic gastrointestinal disorders is of paramount importance to ensure success.
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New approaches to allergen immunotherapy.
Gunawardana, NC, Durham, SR
Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology. 2018;(3):293-305
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OBJECTIVE New insights into mechanisms should enable strategic improvement of allergen immunotherapy, aiming to make it safer, faster, more effective, and able to induce long-term tolerance. We review novel approaches with potential to translate into clinical use. DATA SOURCES Database searches were conducted in PubMed, Scopus, and Google Scholar. STUDY SELECTIONS Search terms were based on current and novel approaches in immunotherapy. Literature was selected primarily from recent randomized double-blinded placebo-controlled trials and meta-analyses. RESULTS Alum, microcrystalline tyrosine, and calcium phosphate are adjuvants in current use. Toll-like receptor-4 agonists combined with allergen have potential to shorten duration of treatment. Other novel adjuvants, nanoparticles, and virus-like particles in combination with allergen have shown early promise. Omalizumab lessens systemic side effects but does not improve efficacy. Intralymphatic immunotherapy for aeroallergens, epicutaneous immunotherapy for food allergens, and use of modified allergens (allergoids), recombinant allergens (and hypoallergenic variants), and T- and B-cell peptide approaches have shown evidence of efficacy and permitted shortened courses but have only rarely been compared with conventional extracts. CONCLUSION Novel routes of immunotherapy, use of modified allergens, and combination of allergens with immunostimulatory adjuvants or immune modifiers have been developed to augment downregulation of T-helper cell type 2 immunity and/or induce "protective" blocking antibodies. Although these strategies have permitted shortened courses, confirmatory phase 3 trials are required to confirm efficacy and safety and head-to-head trials are required for comparative efficacy. Currently, subcutaneous and sublingual immunotherapies using in-house standardized crude extracts remain the only approaches proved to induce long-term tolerance.
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Environmental Food Exposure: What Is the Risk of Clinical Reactivity From Cross-Contact and What Is the Risk of Sensitization.
Sheehan, WJ, Taylor, SL, Phipatanakul, W, Brough, HA
The journal of allergy and clinical immunology. In practice. 2018;(6):1825-1832
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Abstract
For food-allergic individuals, the typical exposure to food proteins happens during ingestion; however, individuals may be exposed to foods in other ways. In addition to ingestion reactions, allergic patients may have reactions from cutaneous or mucosal exposures to food proteins, with the classic example being a peanut-allergic child touching a counter with peanut butter and then rubbing their eyes. Similar to hands, saliva can also act as a carrier for food proteins. Finally, there is a wealth of new research regarding the presence of food proteins in the environment, for example, within household floor dust. This review will focus on (1) cross-contact of food proteins and (2) environmental food protein exposures. Cross-contact occurs when one type of food comes into contact with another type of food resulting in the mixture of proteins. For food allergies, cross-contact is important when an allergen is inadvertently transferred to a food/meal that is thought to not contain that specific allergen. We will discuss the current literature regarding the presence of detectable food proteins in different locations, how and if these proteins are transferred or eliminated, and the clinical implications of exposures to food proteins under these different scenarios.
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Pathophysiology of Eosinophilic Esophagitis.
O'Shea, KM, Aceves, SS, Dellon, ES, Gupta, SK, Spergel, JM, Furuta, GT, Rothenberg, ME
Gastroenterology. 2018;(2):333-345
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Eosinophilic esophagitis is an emerging disease that is distinguished from gastroesophageal reflux disease by the expression of a unique esophageal transcriptome and the interplay of early life environmental factors with distinct genetic susceptibility elements at 5q22 (TSLP) and 2p23 (CAPN14). Rare genetic syndromes have uncovered the contribution of barrier disruption, mediated in part by defective desmosomes and dysregulated transforming growth factor beta production and signaling, to eosinophilic esophagitis pathophysiology. Experimental modeling has defined a cooperative role of activated eosinophils, mast cells, and the cytokines IL-5 and IL-13, mediated by allergic sensitization to multiple foods. Understanding these processes is opening the way to better treatment based on disrupting allergic inflammatory and type 2 cytokine-mediated responses, including anti-cytokine therapeutics and dietary therapy.
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Death by food.
Byard, RW
Forensic science, medicine, and pathology. 2018;(3):395-401
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Abstract
Although death from food is not an uncommon finding in forensic facilities worldwide, the range of underlying lethal mechanisms and associated conditions that should be sought at the time of autopsy is quite disparate. Deaths may occur from i) infectious agents including bacteria, viruses, protozoa, cestodes, nematodes and prions; ii) natural toxins including amanita toxins, tetrodotoxin, ciguatera and scombroid; iii) anaphylaxis; iv) poisoning; v) mechanical issues around airway and gut obstruction and/or perforation; and vi) miscellaneous causes. Food-related deaths are important in terms of global mortality, and thus autopsies need to be comprehensive with full ancillary testing. Medicolegal matters may involve issues concerning likely exposure to infectious agents, possible foods ingested, the declared content and possible components of food, the significance of toxicological analyses, and aspects of duty of care in cases of café coronary syndrome and gastroenteritis while in care.