Search

Summary Food allergies occur due to a lack of tolerance to the proteins found in foods. While IgE‐ and non‐IgE‐mediated food allergies have different clinical manifestations, epidemiology, pathophysiology, and management, they share dysregulated T cell responses. Recent studies have shed light on the contributions of different T cell subsets to the development and persistence of different food allergic diseases. This review discusses the role of T cells in both IgE‐ and non‐IgE‐mediated food allergies and considers the potential future investigations in this context. [ABSTRACT FROM AUTHOR]

This article provides a summary of a Cochrane review on the medical treatment of eosinophilic esophagitis (EoE). EoE is a chronic inflammatory condition of the esophagus that can affect individuals of all ages, but is more common in males and adults. The review evaluated the efficacy and safety of different medical interventions for EoE, including corticosteroids and biologics. The findings suggest that corticosteroids improve clinical and histological outcomes, while biologics may improve clinical outcomes. However, the cost and availability of biologics should be considered. Further research and cost-effectiveness analyses are needed to fully evaluate and compare these treatments. [Extracted from the article]

Background: Eosinophilic esophagitis (EoE) involves a chronic immune‐mediated response to dietary antigens. Recent work identifies T‐cell clonality in children with EoE, however, it is unknown whether this is true in adults or whether there is a restricted food‐specific T‐cell repertoire. We sought to confirm T‐cell receptor (TCR) clonality in EoE and assess for differences with specific food triggers. Methods: Bulk TCR sequencing was performed on mRNA isolated from esophageal biopsies obtained from adults and children with EoE (n = 15) who had food triggers confirmed by endoscopic evaluation. Non‐EoE adult and pediatric controls (n = 10) were included. Differences in TCR clonality by disease and treatment status were assessed. Shared and similar V‐J‐CDR3s were assessed based on specific food triggers. Results: Active EoE biopsies from children but not adults displayed decreased unique TCRα/β clonotypes and increased relative abundance of TCRs comprising >1% of the total compared to non‐EoE controls and paired inactive EoE samples. Among patients in which baseline, post diet elimination, and food trigger reintroduction samples (n = 6) were obtained, we observed ~1% of TCRs were shared only between pre‐diet elimination and trigger reintroduction. Patients with a shared EoE trigger (milk) had a greater degree of shared and similar TCRs compared to patients with differing triggers (seafood, wheat, egg, soy). Conclusion: We confirmed relative clonality in children but not adults with active EoE and identified potential food‐specific TCRs, particularly for milk‐triggered EoE. Further studies are needed to better identify the broad TCR repertoire relevant to food triggers. [ABSTRACT FROM AUTHOR]

Summary: Eosinophils are a common clinical feature associated with chronic allergic diseases, and elemental diets, systemic steroids, anti‐IL‐5 and anti‐IL‐13 treatment have shown some therapeutic promise. Herein, we present evidence that pre‐ and post‐intraperitoneal administration of tacrolimus (FK506) is very effective in reducing CCR3/Siglec‐F+ eosinophils in Aspergillus‐challenged asthma and EoE, CD2‐IL‐5 induced global eosinophilia, and DOX regulated IL‐13‐induced asthma. We used flow cytometry and anti‐major basic protein (MBP) immunostaining to examine eosinophils in the spleen, bone marrow, BALF, lung, oesophagus and intestine. Additionally, we also performed ELISA and Western blot analyses to show that tacrolimus treatment also reduces the levels of eosinophil‐specific cytokines IL‐4, IL‐5, IL‐13 and TGF‐β, eosinophil‐specific chemokines Eotaxin‐1 and Eotaxin‐2, and progenitors of target RCAN1 mRNA and protein levels. Additionally, the current investigations also show that the TGF‐β‐mediated oesophageal and lung fibrosis is also reduced in Aspergillus‐challenged, CD2‐IL‐5 transgenic and DOX‐responsive IL‐13 mice. Mechanistically, we show that tacrolimus in vitro treatment inhibited bone marrow‐derived eosinophil proliferation and viability by promoting eosinophil apoptosis that may be associated with downregulation of RCAN1. Taken together, we provide in vivo and in vitro evidence that tacrolimus ameliorates eosinophil levels and associated pathogenesis in allergen‐, IL‐5‐ and IL‐13‐induced EoE, EG and asthma pathogenesis. Considering tacrolimus side‐effects and reactivity to several other drugs, we propose the topical use of tacrolimus for paediatric and low‐dose oral for adult patients as a novel therapeutic strategy for the clinical trial to reduce mucosal eosinophilia first in steroid‐refractory or elemental diet non‐responsive adult EoE, EG and asthma patients. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with EoE manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (IgE) is directed, if any, have not yet been characterized. Methods: Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of EoE. Specific IgE (sIgE) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal IgE response and IgG4 to food allergens, were measured. Results: There was no difference in total IgE harvested between the 2 biopsy methods (p > 0.05) or between the EoE‐positive (N = 12) and EoE‐negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum IgE to any of the airborne or food proteins tested, but low levels of IgE specific to Candida and Staphylococcus enterotoxins were detected. Low levels of IgG4 specific to wheat, soy, peanut, and egg were also detected. Conclusions: Both MBB and STB are able to harvest measureable levels of IgE and IgG4 from the esophageal mucosa. Low levels of serum‐specific IgE suggest that other inflammatory mechanisms, besides type I, IgE‐mediated, allergen‐specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both IgE‐mediated and non‒IgE‐mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia. [ABSTRACT FROM AUTHOR]

Background: The pathogenesis of eosinophilic esophagitis (EoE) is currently unknown, but evidence suggests that allergic sensitization to food and airborne allergens may play a key role. This retrospective study examines the rate of sensitization to both food and airborne allergens in EoE patients, and compares their sensitivity patterns to control groups. Methods: We identified 103 patients with a diagnosis of EoE via esophageal eosinophilia (≥15 eosinophils/high‐power field [hpf]), who had undergone comprehensive food and/or airborne allergen testing through either skin or in vitro methods. Food and airborne allergen sensitization was defined as positive testing in at least 1 food subgroup (milk, peanut, tree nut, seafood/fish, soy, grain, egg) or airborne subgroup (tree, grass, weed, mite/cockroach, animal, mold), respectively. The same sensitization criterion was applied to allergic rhinitis (AR) patients, with and without a clinical suspicion of food allergy (FA), in order to create control groups. Results: Sensitization in the EoE group to at least 1 subgroup of food allergen and airborne allergen was seen in 77.1% (64/83) and 71.7% (38/53), respectively (p = 0.82). There were significant differences in sensitization between EoE and control groups for tree nut, soy, grain, and egg, but no differences noted in any of the other food or airborne allergen subgroups, even after accounting for age and gender. Conclusion: EoE and control groups had similar airborne allergen sensitization patterns, yet dissimilar food allergen sensitization patterns, suggesting that specific allergens may play a more prominent role in the pathogenesis of EoE. The EoE group had a more uniform distribution pattern for food allergens, compared to controls. [ABSTRACT FROM AUTHOR]

Background and aims Current research outcomes in paediatric eosinophilic oesophagitis (EoE) are directed towards histological improvement with no attention to health-related quality of life (HRQOL). The primary objective of this study was to identify key patient-reported and parent proxy outcome elements of EoE disease-specific HRQOL. Methods The research team comprised clinical allergists and gastroenterologists with expertise in paediatric EoE as well as two PhD psychologists with extensive experience in qualitative research. Focused interview techniques were adapted from the Pediatric Quality of Life Inventory 4.0™ methodology and the consolidated criteria for reporting qualitative research. A semi-structured interview guide of open-ended questions was developed, and extensive review of audio-taped transcripts was performed. Results A total of 42 focus interviews were conducted. Child self-reports were obtained for patients in the 5-7, 8-12 and 13-18 years of age groups, and parent proxy reports were obtained in the 2-4, 5-7, 8-12 and 13-18 years of age groups. We discovered that patients and parents often had different concerns, illustrating unique aspects of EoE-specific HRQOL that were not captured in generic HRQOL instruments. Specific themes that emerged from these interviews included, but are not limited to: feelings of being different than family and peers, diet and medication adherence, difficulties with eating food and worry about symptoms and illness. Conclusion Paediatric EoE patient and parent proxy interviews revealed many EoE-specific aspects of HRQOL that are not captured in generic HRQOL instruments. Outcome measures that reflect patient- and parent proxy-reported HRQOL are a critical need in paediatric EoE. [ABSTRACT FROM AUTHOR]