Food-specific IgG4 is associated with eosinophilic esophagitis.
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ABSTRACT:
SUBMITTER: Wright BL
PROVIDER: S-EPMC5053831 | biostudies-literature | 2016 Oct
REPOSITORIES: biostudies-literature
Publications
Food-specific IgG<sub>4</sub> is associated with eosinophilic esophagitis.
Wright Benjamin L BL Kulis Mike M Guo Rishu R Orgel Kelly A KA Wolf W Asher WA Burks A Wesley AW Vickery Brian P BP Dellon Evan S ES
The Journal of allergy and clinical immunology 20160406 4
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Project description:BackgroundLinks between food allergens and eosinophilic esophagitis (EoE) have been established, but the interplay between EoE- and IgE-associated immediate hypersensitivity to foods remains unclear.ObjectiveWe sought to determine the prevalence of IgE-associated food allergy at the time of diagnosis of EoE in children and to determine whether differences existed in presentation and disease compared to subjects with EoE alone.MethodsEosinophilic esophagitis patients were stratified based on the diagnosis of IgE-associated immediate hypersensitivity (EoE + IH vs. EoE-IH). Clinical, histologic, pathologic, and endoscopic differences were investigated using a retrospective database.ResultsWe found that 29% of the 198 EoE patients in our cohort had EoE + IH. These subjects presented at a younger age than those without IH (6.05 vs. 8.09 years, P = 0.013) and were more likely to have comorbid allergic disease. Surprisingly, the EoE + IH group presented with significantly different clinical symptoms, with increased dysphagia, gagging, cough, and poor appetite compared to their counterparts in the EoE-IH group. Male gender, allergic rhinitis, the presence of dysphagia, and younger age were independently associated with having EoE + IH. Specific IgE levels to common EoE-associated foods were higher in EoE + IH, regardless of eliciting immediate hypersensitivity symptoms. In contrast, IgE levels for specific foods triggering EoE were relatively lower in both the groups than IgE levels for immediate reactions.Conclusions and clinical relevanceImmediate hypersensitivity is common in children with EoE and identifies a population of EoE patients with distinct clinical characteristics. Our study describes a subtype of EoE in which IgE-mediated food allergy may impact the presentation of paediatric EoE.
| S-EPMC5085872 | biostudies-literature
Project description:IntroductionHigh levels of serum food-specific IgG4 (sIgG4) have been reported in patients with EoE. The objective of this study was to examine whether serum sIgG4 levels to foods and aeroallergens are higher in EoE patients than allergic controls and to investigate the association between sIgG4 and EoE clinical characteristics.MethodsThis was a case-control study nested in a prospective EoE Cohort. EoE cases were defined per consensus guidelines, and controls were individuals with symptoms who were confirmed to be EoE-negative on upper endoscopy. Demographic and clinical information was prospectively collected. Serum IgE and sIgG4 were measured to foods and aeroallergens by ImmunoCAP. Mean levels of sIgG4 were compared between cases and controls, and logistic regression models were used to examine predictors of elevated milk sIgG4 levels.ResultsThe analysis included 123 individuals (EoE n = 93, control n = 30) with a similar distribution of allergic disease between EoE patients and controls (86% vs. 93%; p = .30). EoE patients had significantly higher sIgG4 levels to all allergens evaluated, with the exception of birch (p = .24). Milk sIgG4 levels were independently associated with milk consumption (OR 4.95; p = .01) and the presence of sIgE to milk (OR 4.23; p = .008).ConclusionSerum sIgG4 levels to food and aeroallergen proteins were higher in patients with EoE than non-EoE controls, and higher levels of milk sIgG4 were independently associated with milk consumption and the presence of sIgE to milk proteins. Whether sIgG4 plays a pathogenic role in EoE or could be used as an EoE biomarker remains unknown and warrants further study.
| S-EPMC9938092 | biostudies-literature
Project description:ObjectiveThe aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls.MethodsWe conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons.ResultsOne hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls.ConclusionsDominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.
| S-EPMC10201396 | biostudies-literature
Project description:ObjectiveTo review the understanding of the pathogenesis of eosinophilic esophagitis (EoE) and the role of the immune system in the disease process.Data sourcesPeer-reviewed articles on EoE from PubMed searching for "Eosinophilic Esophagitis and fibrosis" in the period of 1995 to 2013.Study selectionsStudies on the clinical and immunologic features, pathogenesis, and management of EoE.ResultsRecent work has revealed that thymic stromal lymphopoietin and basophil have an increased role in the pathogenesis of disease. Additional understanding on the role of fibrosis in EoE is emerging.ConclusionThe incidence of EoE is increasing like most atopic disease. Similar to other allergic diseases, EoE is treated with topical steroids and/or allergen avoidance.
| S-EPMC4332835 | biostudies-literature
Project description:BackgroundEosinophilic 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.MethodsBulk 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.ResultsActive 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).ConclusionWe 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.
| S-EPMC10768854 | biostudies-literature
Project description:BackgroundEvaluation of IgE-mediated food sensitivity is frequently performed for patients with eosinophilic esophagitis (EoE). However, the clinical relevance of identifying IgE-mediated sensitivity to foods in adults is unclear.ObjectiveTo determine whether EoE associated with food or aeroallergen sensitivity represents a phenotype of EoE with distinct clinical or biological features.MethodsA medical record review identified 257 patients with a diagnosis of EoE evaluated in the adult allergy clinic at the University of Wisconsin Hospital and Clinics from 2008 to 2013. Patient records were reviewed to capture measures of disease severity, endoscopy results, pathology reports, allergy testing, medical management and patient-reported outcomes.ResultsEvaluation of food sensitization with skin prick testing and/or serum IgE was performed for 93% of patients. Sensitization to at least 1 food was identified in 54% of patients who were more likely to report concomitant asthma, allergic rhinitis, eczema, and/or food allergy compared with nonfood sensitive patients. Aeroallergen sensitivity was identified in 87% of patients tested. Clinical characteristics, including EoE symptoms, disease severity, endoscopic findings, peripheral eosinophilia, and patient-reported outcomes, did not differ between food sensitive and non-food sensitive patients. However, on endoscopy, aeroallergen sensitive patients were more likely to have strictures and less likely to exhibit felinization compared with non-aeroallergen sensitized patients.ConclusionAdults with EoE and IgE-mediated food sensitivity are not phenotypically different than non-food sensitive patients. There is no clear clinical utility in identifying food sensitivity in adults with EoE. Further studies are needed to determine whether aeroallergen sensitivity represents a distinct phenotype of EoE.
| S-EPMC5065768 | biostudies-literature
Project description: Not available
| S-EPMC10098655 | biostudies-literature
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.
| S-EPMC6448398 | biostudies-literature
Project description:IntroductionUnder homeostatic conditions, esophageal epithelium displays a proliferation/differentiation gradient that is generated as proliferative basal cells give rise to suprabasal cells then terminally differentiated superficial cells. This proliferation/differentiation gradient is often perturbed in esophageal pathologies. Basal cell hyperplasia may occur in patients with gastroesophageal reflux disease (GERD), a condition in which acid from the stomach enters the esophagus, or eosinophilic esophagitis (EoE), an emerging form of food allergy. While GERD is a primary risk factor for esophageal cancer, epidemiological data suggests that EoE patients do not develop esophageal cancer.MethodsIn order to investigate the impact of EoE and esophageal cancer specifically on the cellular landscape of esophageal epithelium, we perform single cell RNA-sequencing in murine models of EoE and esophageal cancer, specifically esophageal squamous cell carcinoma (ESCC). We further evaluate modules of co-expressed genes in EoE- and ESCC-enriched epithelial cell clusters. Finally, we pair EoE and ESCC murine models to examine the functional relationship between these pathologies.ResultsIn mice with either EoE or ESCC, we find expansion of cell populations as compared to normal esophageal epithelium. In mice with EoE, we detect distinct expansion of 4 suprabasal populations coupled with depletion of 2 basal populations. By contrast, mice with ESCC display unique expansion of 2 basal populations and 1 suprabasal population, as well as depletion of 2 suprabasal populations. Senescence, glucocorticoid receptor signaling, and granulocyte-macrophage colony-stimulating factor pathways are associated with EoE-enriched clusters while pathways associated with cell proliferation and metabolism are identified in ESCC-enriched clusters. Finally, our in vivo data demonstrate that exposure to EoE inflammation limits tumor burden of esophageal carcinogenesis.DiscussionOur findings provide the first functional investigation of the relationship between EoE and esophageal cancer and suggest that esophageal epithelial remodeling events occurring in response to EoE inflammation may limit esophageal carcinogenesis. This investigation may have future implications for leveraging allergic inflammation-associated alterations in epithelial biology to prevent and/or treat esophageal cancer.
| S-EPMC10090679 | biostudies-literature