Dataset Information

Food allergen triggers are increased in children with the TSLP risk allele and eosinophilic esophagitis.

ABSTRACT:

Objectives

TSLP has been shown to be associated with eosinophilic esophagitis (EoE). Specifically, children with EoE often have the nucleotides AA or AG instead of GG at the single nucleotide polymorphism position RS3806932. Presently, the phenotypic characteristics in EoE children with the TSLP EoE risk allele are unknown.

Methods

A retrospective analysis was performed of all children with EoE who had TSLP genotyping at The Children's Hospital of Philadelphia from 2008-2014. EoE food allergen triggers, presence of atopic features, IgE mediated food allergy and skin prick testing results were reviewed. The number and type of EoE food allergen triggers were compared with genotype using chi-square analysis. Primary cell cultures from EoE patients with or without the risk allele were stimulated with ovalbumin and TSLP secretion was measured by ELISA.

Results

Fifty three of 309 patients were found to have no copies of the TSLP risk allele, whereas 256 patients were found to have one or more copies of the risk allele. There was an increase in the number of patients with three or more EoE food allergens among those who were either homozygous or heterozygous for the risk allele compared to those without the risk allele (P?ConclusionsThe TSLP risk allele is associated with having multiple EoE food allergen triggers. This novel EoE genotypic-phenotypic correlation may guide future treatment for those with the TSLP risk allele.

SUBMITTER: Fahey LM

PROVIDER: S-EPMC5862152 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Food allergen triggers are increased in children with the TSLP risk allele and eosinophilic esophagitis.

Fahey Lisa M LM Chandramouleeswaran Prasanna M PM Guan Shaobo S Benitez Alain J AJ Furuta Glenn T GT Aceves Seema S SS Wang Mei-Lun ML Liacouras Chris A CA Muir Amanda B AB Sleiman Patrick Ma PM Hakonarson Hakon H Spergel Jonathan M JM Cianferoni Antonella A

Clinical and translational gastroenterology 20180306 3

<h4>Objectives</h4>TSLP has been shown to be associated with eosinophilic esophagitis (EoE). Specifically, children with EoE often have the nucleotides AA or AG instead of GG at the single nucleotide polymorphism position RS3806932. Presently, the phenotypic characteristics in EoE children with the TSLP EoE risk allele are unknown.<h4>Methods</h4>A retrospective analysis was performed of all children with EoE who had TSLP genotyping at The Children's Hospital of Philadelphia from 2008-2014. EoE ...[more]

PMID: 29511165

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Project description:BackgroundIn children with eosinophilic esophagitis (EoE) foods are the most common disease triggers, but environmental allergens are also suspected culprits.ObjectiveTo determine the effects of environmental allergen sensitization on response to treatment in children with EoE in the southeastern United States.MethodsPatients 2 to 18 years old who were referred to the Arkansas Children's Hospital Eosinophilic Gastrointestinal Disorders Clinic from January 2012 to January 2016 were enrolled in a prospective, longitudinal cohort study with collection of demographics, clinical symptoms, medical history, allergy sensitization profiles, and response to treatment over time. Comparisons were made between complete responders (peak esophageal eosinophil count <15 per high-power field [HPF]) and nonresponders (>25 eosinophils per HPF) after treatment with diet elimination alone, swallowed corticosteroids alone, or diet elimination and swallowed corticosteroids. Sensitization patterns to environmental allergens found in the southeastern United States were analyzed for the effect on treatment response.ResultsA total of 223 individuals were enrolled. Of these, 182 had environmental allergy profiling and at least one endoscopy while receiving proton pump inhibitor (PPI) therapy. Twenty-nine individuals had PPI-responsive EoE and were excluded from further analysis, leaving 123 individuals with non-PPI-responsive EoE who were further analyzed; 72 (58.5%) were complete responders and 33 (26.8%) were nonresponders. Seventeen individuals (13.8%) were partial responders (≥1 but ≤25 eosinophils per HPF) and excluded from further analysis. Nonresponders were more likely to be sensitized to perennial allergens (P = .02). There was no significant difference in response based on seasonal allergen sensitization. Individuals with mold or cockroach sensitization were more likely to fail combination diet and swallowed corticosteroid treatment (P = .02 and P = .002).ConclusionPerennial allergen and mold sensitization may lead to nonresponse to EoE treatment in some patients. Additional studies are needed to further understand the effect of environmental allergens on EoE.Trial registrationClinicalTrials.gov identifier: NCT01779154.

Project description:Background & aimsA 6-food elimination diet induces remission in most children and adults with eosinophilic esophagitis (EoE). The effectiveness of empiric elimination of only 4 foods has not been studied in children. We performed a prospective observational outcome study in children with EoE treated with dietary exclusion of cow's milk, wheat, egg, and soy. The objective was to assess the clinical, endoscopic, and histologic efficacy of this treatment in EoE.MethodsWe recruited children (1-18 years old, diagnosed per consensus guidelines) from 4 medical centers. Study participants (n = 78) were given a proton pump inhibitor twice daily and underwent a baseline esophagogastroduodenoscopy. Subjects were instructed on dietary exclusion of cow's milk, wheat, egg, and soy. Clinical, endoscopic, and histologic assessments were made after 8 weeks. Responders had single foods reintroduced for 8 weeks, with repeat endoscopy to assess for recurrence of active disease. The primary endpoint was histologic remission (fewer than 15 eosinophils per high-powered field). Secondary endpoints included symptom and endoscopic improvements and identification of foods associated with active histologic disease.ResultsAfter 8 weeks on 4-food elimination diet, 50 subjects were in histologic remission (64%). The subjects' mean baseline clinical symptoms score was 4.5, which decreased to 2.3 after 8 weeks of 4-food elimination diet (P < .001). The mean endoscopic baseline score was 2.1, which decreased to 1.3 (P < .001). After food reintroduction, the most common food triggers that induced histologic inflammation were cow's milk (85%), egg (35%), wheat (33%), and soy (19%). One food trigger that induced recurrence of esophageal inflammation was identified in 62% of patients and cow's milk-induced EoE was present in 88% of these patients.ConclusionsIn a prospective study of children with EoE, 8 weeks of 4-food elimination diet induced clinical, endoscopic, and histologic remission in more than 60% of children with EoE. Although less restrictive than 6-food elimination diet, 4-food elimination diet was nearly as effective, and can be recommended as a treatment for children with EoE.

Project description:BACKGROUND:Eosinophilic esophagitis (EoE) is a chronic immune-mediated inflammatory disorder and represents the leading cause of food impaction. The pathogenesis of EoE is the result of an interplay between genetic, environmental and host immune system factors. New therapeutic approaches for EoE have been proposed. In this manuscript we review the current evidence regarding EoE management in pediatric age, with a particular focus on new findings related to the efficacy and safety of monoclonal antibodies. MAIN BODY:Conventional therapies have failed in treating some patients with EoE, which then requires aggressive procedures such as esophageal dilatation. The most effective available medical therapy for EoE is swallowed topic corticosteroids (fluticasone propionate and budesonide), which have two main drawbacks: they are related to well-known adverse effects (especially in the paediatric population), and there are not enough long-term data to confirm that they are able to reverse the remodelling process of the esophageal mucosa, which is the major cause of EoE symptoms (including dysphagia, abdominal pain, nausea, obstruction, perforation and vomiting). The monoclonal antibodies appear to be an interesting therapeutic approach. However, the studies conducted until now have shown substantial histological improvement not coupled with significant clinical improvements and no significant relationship between a decreasing number of eosinophils and clinical symptoms, highlighting the importance in the pathogenesis of EoE of cells such as T-helper cells, mast cells, B cells, epithelial cells and natural killer cells. CONCLUSIONS:Monoclonal antibodies targeting a signal involved in the pathogenesis of EoE may not break the complex self-propagating inflammatory activation responsible for perpetuation of the inflammatory response and the development of symptoms and complications. We speculate that combined biological therapies targeting more than one molecule or cell may provide better results, with conventional therapies potentially enhancing the effects of antibodies. However, further studies should aim to find the best therapeutic approach to target the cells involved in the remodelling process and to reverse the histological changes in this complex clinical condition.

Dataset Information

Food allergen triggers are increased in children with the TSLP risk allele and eosinophilic esophagitis.

Objectives

Methods

Results

Publications

Food allergen triggers are increased in children with the TSLP risk allele and eosinophilic esophagitis.

Similar Datasets

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