The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy all over the world and manifestations of food allergy appear increasingly frequent also in elderly subjects. Environmental and nutritional changes have partly changed the epidemiology of allergic reactions to foods and new food allergic syndromes have emerged in recent years. The deepening of the study of the intestinal microbiota has highlighted important mechanisms of immunological adaptation of the mucosal immune system to food antigens, leading to a revolution in the concept of immunological tolerance. As a consequence, new prevention models and innovative therapeutic strategies aimed at a personalized approach to the patient affected by food allergy are emerging. This review focuses on these new perspectives and their practical implications in the management of food allergy, providing an updated view of this complex pathology.

https://www.mdpi.com/1422-0067/21/4/1474/pdf

New Perspectives in Food Allergy

Eosinophils play homeostatic roles in different tissues and are found in several organs at a homeostatic baseline, though their tissue numbers increase significantly in development and disease. The morphological, phenotypical, and functional plasticity of recruited eosinophils are influenced by the dynamic tissue microenvironment changes between homeostatic, morphogenetic, and disease states. Activity of the epithelial-mesenchymal interface, extracellular matrix, hormonal inputs, metabolic state of the environment, as well as epithelial and mesenchymal-derived innate cytokines and growth factors all have the potential to regulate the attraction, retention, in situ hematopoiesis, phenotype, and function of eosinophils. This review examines the reciprocal relationship between eosinophils and such tissue factors, specifically addressing: (1) tissue microenvironments associated with the presence and activity of eosinophils; (2) non-immune tissue ligands regulatory for eosinophil accumulation, hematopoiesis, phenotype, and function (with an emphasis on the extracellular matrix and epithelial-mesenchymal interface); (3) the contribution of eosinophils to regulating tissue biology; (4) eosinophil phenotypic heterogeneity in different tissue microenvironments, classifying eosinophils as progenitors, steady state eosinophils, and Type 1 and 2 activated phenotypes. An appreciation of eosinophil regulation by non-immune tissue factors is necessary for completing the picture of eosinophil immune activation and understanding the functional contribution of these cells to development, homeostasis, and disease.

https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1002/JLB.1MR1117-442RR

Shaping eosinophil identity in the tissue contexts of development, homeostasis, and disease

Over the past decade, the role of proton pump inhibitor (PPI) medication has evolved from a diagnostic tool for Eosinophilic Esophagitis (EoE), by excluding patients with PPI responsive esophageal eosinophilia (PPI-REE), to a therapy for EoE. This transition resulted from the Updated International Consensus Diagnostic Criteria for Eosinophilic Esophagitis: Proceedings of the Appraisal of Guidelines for Research and Evaluation II (AGREE) Conference to support PPI therapy for EoE in children and adults. Additional recent advances have suggested a role for genetic variations that might impact response to PPI therapy for EoE. This review article will explore a brief background of EoE, the evolution of PPI therapy for EoE and its proposed mechanisms, efficacy and safety in children and adults, and considerations for future PPI precision medicine in patients with EoE. 

/pdf/proton-pump-inhibitor-therapy-for-eosinophilic-esophagitis-3s9znzb3.pdf

Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions

Neuroimmune interplay during type 2 inflammation: symptoms, mechanisms and therapeutic targets in atopic diseases.

The prevalence of food allergies is increasing worldwide. To understand the regional specificities of food allergies and develop effective therapeutic interventions, extensive regional epidemiological studies are necessary. While data regarding incidence, prevalence, regional variation, and treatment in food allergies are available for western countries, such studies may not be available in many Asian countries. China accounts for almost 20% of the world's population and has a vast ethnic diversity, but large-scale meta-analyses of epidemiological studies of food allergy in China are lacking. A literature search revealed 22 publications on the prevalence of food allergy in Chinese populations. A review of these studies showed that the prevalence of food allergies in China is comparable to that in western countries, even though the Chinese diet is vastly different from that of the West and may vary even greatly within China, and finally, specific antigenic triggers of food allergy vary between China and the West and also within China. Current clinical management of food allergy in China includes allergen-specific immunotherapy, Chinese herbal medicine, acupuncture, and Western medicine. This study demonstrates an unmet need in China for a thorough investigation of the prevalence of food allergies in China, the specific foods involved, and characterization of the specific antigenic triggers of food allergy with respect to ethnicity, age, and diet in China.

Regional Differences in Food Allergies

Eosinophilic esophagitis (EoE) is an immune-mediated, chronic esophageal disease characterized by esophageal symptoms and esophageal eosinophilia. It is triggered by foods and possibly by environmental allergens. Currently, there are no FDA-approved therapies for EoE. Commonly used treatments include dietary restrictions and topical corticosteroids. Many of these therapies are suboptimal in their efficacy, have side effects, or diminish patients' quality of life. Biologic therapies for EoE have therefore been sought as an alternative. The mechanism by which food allergens trigger EoE is thought to be a T helper type 2 (Th2) reaction, resulting in secretion of the cytokines IL-4, IL-5, and IL-13. IL-5 induces eosinophil production and trafficking to the esophagus, and IL-13 induces esophageal epithelial cells to secrete eotaxin-3, which drives eosinophil chemotaxis and activation. Mepolizumab and reslizumab, two anti-IL-5 antibodies, were studied in children and adults with EoE and resulted in reduction of esophageal tissue and blood eosinophils, but no significant reduction in symptoms. QAX576, an anti-IL-13 antibody, was studied in adults with EoE and showed a decrease in the esophageal eosinophil load and a trend towards clinical improvement. Since in situ IgE production was demonstrated in the EoE esophagus, omalizumab, an anti-IgE antibody, was studied in patients with EoE and not found to be overall beneficial. Furthermore, given the increased esophageal epithelial cell TNF-α expression in EoE, infliximab, an anti-TNF-α antibody, was studied in patients with EoE, with lack of success both clinically and histologically. In summary, although none of the biologicals studied so far in EoE have been highly effective, many demonstrated some histological benefit, especially those that targeted the Th2 axis. Therefore, the future for biologicals is promising as the pathophysiology of EoE is better understood, clinical assessment tools are validated, identification of patient subsets that respond best to biologicals is made, and dosages of biologicals are optimized.

Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?

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Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?