Deeper Than the Epithelium: Role of Matrix and Fibroblasts in Pediatric and Adult Eosinophilic Esophagitis.
Ontology highlight
ABSTRACT:
SUBMITTER: Nguyen N
PROVIDER: S-EPMC4965178 | biostudies-literature | 2016 Aug
REPOSITORIES: biostudies-literature
Publications
Deeper Than the Epithelium: Role of Matrix and Fibroblasts in Pediatric and Adult Eosinophilic Esophagitis.
Nguyen Nathalie N Furuta Glenn T GT Masterson Joanne C JC
Journal of pediatric gastroenterology and nutrition 20160801 2
Similar Datasets
Project description:Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus that occurs in both children and adults. Previous studies of affected tissue from pediatric cohorts have identified prominent signatures of eosinophilia and type 2 inflammation. However, the details of the immune response in adults with EoE are still being elucidated. To determine whether EoE in adults shares inflammatory profiles with those observed in children, we performed RNA sequencing of paired human esophageal biopsies and blood samples from adults with EoE or gastroesophageal reflux disease. Unbiased analysis of differentially expressed genes in tissue revealed a strong IFN signature that was significantly enriched in EoE patients as compared with patients with gastroesophageal reflux disease. Both type I and type II IFN-responsive genes were upregulated in adult biopsies, but not in blood. A similar increase in expression of IFN gene sets was observed in pediatric EoE biopsies as compared with non-EoE samples, and in public pediatric and adult RNA-sequencing data. Finally, we found that human peripheral CD4+ T cells from children with EoE produce IFN-γ upon activation with EoE-causal allergens. Together, this work identifies a conserved IFN signature in pediatric and adult EoE, highlighting a role for non-type 2 inflammatory networks in the disease process in humans.
| S-EPMC7946729 | biostudies-literature
Project description:Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus that occurs in both children and adults. Previous studies of affected tissue in pediatric cohorts have identified prominent signatures of eosinophilia and type 2 inflammation. However, the details of the immune response in adults with EoE are still being elucidated. To determine whether EoE in adults shares inflammatory profiles with those observed in children, we performed RNA-sequencing of paired esophageal biopsies and blood samples from adults with EoE or gastroesophageal reflux disease (GERD). Unbiased analysis of differentially expressed genes in tissue revealed a strong interferon signature that was significantly enriched in EoE patients as compared to patients with GERD. Both type I and type II interferon responsive genes were upregulated in adult biopsies, but not in blood. A similar increase in expression of interferon gene sets was observed in pediatric EoE biopsies as compared to non-EoE samples, and in public pediatric and adult RNA-sequencing data. Finally, we found that peripheral CD4+ T cells from children with EoE produce IFNG upon activation with EoE-causal allergens. Together, this work identifies a conserved interferon signature in pediatric and adult EoE, highlighting a role for non-type 2 inflammatory networks in the disease process.
2020-08-22 | GSE156651 | GEO
Project description:Given the chronic and progressive course of eosinophilic esophagitis (EoE), patients with pediatric-onset EoE will require uninterrupted gastroenterology (GI) care as they reach adulthood. Yet, the effectiveness of transferring and integrating EoE patients from pediatric GI (pGI) to adult GI (aGI) care has not been studied. To address this gap, we assessed loss to follow-up, duration from the last pGI to the first aGI encounters (clinic visit and EGD), and its impact on clinical course and medication non-adherence in EoE patients. We identified 58 EoE patients who initially received pGI care and were transferred to aGI between 2017 and 2023 within our institution's shared electronic medical record environment. Demographic, clinical, endoscopic, and histologic data were analyzed using descriptive statistics, survival analysis, Cox regression models, and paired comparisons. Loss to follow-up was 16%. The median duration from the last pGI clinic visit to the first aGI clinic visit was 299 days, and that for the last pGI EGD to the first aGI EGD was 730 days. A significantly higher odds of heartburn (McNemar P-value = 0.01) and higher medication non-adherence rates (7% vs. 26%) were noted in 49 patients who established care with the aGI. The endoscopic and histologic severity remained unchanged. In EoE patients, transferring from pGI to aGI care is associated with loss of follow-up, deterioration of symptoms, and medication non-adherence. There is a critical need to develop optimized protocols to ensure a seamless transfer of care for EoE patients.
| S-EPMC11878569 | biostudies-literature
Project description:Treatment of eosinophilic esophagitis has progressed from elemental formula for children and esophageal dilation for adults to selective exclusion of food triggers and swallowed topical corticosteroids. Management guidelines are available from the American Gastroenterological Association and the Joint Task Force on Allergy Immunology Practice Parameters. We cannot, however, evaluate the efficacy of treatments without a definition of response. We propose a treat-to-target approach, based on symptoms and findings from endoscopy and histology. This approach addresses dissociations between outcomes, such as symptom persistence despite normalization of histologic features and symptom resolution after esophageal dilation despite histologic features of active disease. Eosinophilic esophagitis can now be treated with biologic agents that target specific immune pathways, and findings from prospective trials have indicated that less-restrictive, empiric, elimination diets can be effective and reduce the need for repeated endoscopic assessment of disease activity during food reintroduction. We also discuss eosinophilic esophagitis subtypes, factors associated with disease, and advances in management.
| S-EPMC8063595 | biostudies-literature
Project description:Subepithelial fibrosis occurs in a subset of eosinophilic esophagitis (EoE) patients and is associated with esophageal stricture. While mechanisms driving EoE fibrosis remain incompletely understood, findings from experimental systems support roles for epithelial-fibroblast crosstalk in this type of tissue remodeling. The current paradigm presents EoE as a progressive fibrostenotic disease in which aged patients develop fibrosis as a function of disease chronicity. In the current study we provide evidence that altered epithelial biology in the aging esophagus may also contribute to EoE-associated fibrosis. We find that induction of EoE inflammation in young and aged mice using the MC903/Ovalbumin protocol for the same time period results in increased lamina propria thickness uniquely in aged animals. Additionally, epithelial cells from aged mice less efficiently limit fibroblast contractility in collagen plug contraction assays compared to those from their young counterparts. Finally, to identify potential mechanisms through which aged esophageal epithelial cells may stimulate fibrotic remodeling, we perform cytokine array experiments in young and aged mice. These studies are significant as identification of age-associated factors that contribute to fibrotic remodeling may aid in the design of strategies toward early detection, prevention, and therapy of fibrostenotic EoE.
| S-EPMC9798296 | biostudies-literature
Project description:Clinical experiences and recent studies suggest that eosinophilic esophagitis (EoE) has the potential to induce caregiver (CG) and child stress. The specific sources of CG EoE-related stress remain uncertain. To address this, we performed a survey of CGs and youth attending a patient with EoE education symposium that measured potential stressful elements in their daily life. Our results indicated that CGs experienced most stress associated with purchasing, preparation, and completion of meals. We conclude that providers should consider this in choosing therapeutic approaches for children with EoE.
| S-EPMC5449262 | biostudies-literature
Project description:RationaleData on the prevalence of mental distress among adult eosinophilic esophagitis (EoE) patients are scarce. Also, a significant gap remains in the understanding of which determinants are related to significant psychological symptoms and whether distressed patients require and receive mental care.MethodsAdult EoE patients were invited to complete standardized measures on anxiety/depressive symptoms (HADS) and general psychopathology (SCL-90-R). All scores were compared to general population norms. Socio-demographic and clinical factors were assessed.ResultsIn total, 147 adult EoE patients (61% males, age 43 (IQR 29-52) years were included (response rate 71%). No difference with general population values was found for total anxiety and depressive symptoms (7.8 ± 6.6 vs. 8.4 ± 6.3; p = 0.31). A total of 38/147(26%) patients reported high levels of anxiety and/or depressive symptoms (HADS-A ≥ 8: 35/147(24%) and HADS-D ≥ 8: 14/147(10%)), indicative of a possible psychiatric disorder. In a multivariate analysis, age between 18-35 years was independently associated with high levels of anxiety (HADS-A ≥ 8) (OR 3.0, 95% CI 1.3-6.9; p = 0.01). The SCL-90-R Global Severity Index (GSI) was significantly higher compared to the general population (p < 0.001). Significant signs of general mental distress (GSI ≥ 80th percentile) were observed in 51(36%) EoE patients, of which 29(57%) patients denied having any mental problems and only 8(16%) patients received mental care.ConclusionA considerable proportion of adult EoE patients suffers from mental distress, with a 3-fold risk of significant anxiety in those patients younger than 35 years. Therefore, population-based studies are required and a proactive approach in the screening for and treatment of these psychological symptoms in EoE practice seems essential.
| S-EPMC8365712 | biostudies-literature
Project description:Adult Eosinophilic Esophagitis Registry Atlas
| PRJNA1083652 | ENA
Project description:Adult Eosinophilic Esophagitis Registry Atlas
| PRJNA1083653 | ENA
Project description:Background & aimsThe nature of the involvement of esophageal tissue in eosinophilic esophagitis (EoE) is unclear. We estimated the intrabiopsy site agreements of the EoE Histologic Scoring System (EoEHSS) scores for the grade (degree) and stage (extent) of involvement of the esophageal epithelial and lamina propria and examined if the EoE activity status influenced the intrabiopsy site agreement.MethodsDemographic, clinical, and EoEHSS scores collected as part of the prospective Outcome Measures for Eosinophilic Gastrointestinal Diseases Across Ages study were analyzed. A weighted Cohen's kappa agreement coefficient (k) was used to calculate the pairwise agreements for proximal:distal, proximal:middle, and middle:distal esophageal biopsy sites, separately for grade and stage scores, for each of the 8 components of EoEHSS. A k > 0.75 was considered uniform involvement. Inactive EoE was defined as fewer than 15 eosinophils per high-powered field.ResultsEoEHSS scores from 1263 esophageal biopsy specimens were analyzed. The k for the stage of involvement of the dilated intercellular spaces across all 3 sites in inactive EoE was consistently greater than 0.75 (range, 0.87-0.99). The k for lamina propria fibrosis was greater than 0.75 across some of the biopsy sites but not across all 3. Otherwise, the k for all other features, for both grade and stage, irrespective of the disease activity status, was 0.75 or less (range, 0.00-0.74).ConclusionsExcept for the extent of involvement of dilated intercellular spaces in inactive EoE, the remaining epithelial features and lamina propria are involved unevenly across biopsy sites in EoE, irrespective of the disease activity status. This study enhances our understanding of the effects of EoE on esophageal tissue pathology.
| S-EPMC10518022 | biostudies-literature