Search

Background: A combination of proton‐pump inhibitors (PPI) and topical steroids (TS) is used to treat children with eosinophilic esophagitis (EoE). However, a subset of children do not respond to this combination therapy. We aimed to identify the esophageal transcriptional, cell composition, and microbial differences between the non‐responders (EoE‐PPI‐TSnr; n = 7) and responders (EoE‐PPI‐TSr; n = 7) to the combination therapy for EoE and controls (n = 9) using metatranscriptomics. Methods: Differential gene expression analysis was used to identify transcriptional differences, validated using the EoE diagnostic panel (EDP). Deconvolution analysis was performed to identify differences in their cell type composition. Microbiome analysis was conducted from esophageal biopsies RNAseq data, and microbial abundance was correlated with esophageal gene expression. Results: In all, 3164 upregulated and 3154 downregulated genes distinguished EoE‐PPI‐TSnr from EoE‐PPI‐TSr. Eosinophilic inflammatory response, cytokine signaling, and collagen formation pathways were significantly upregulated in EoE‐PPI‐TSnr. There was a 56% overlap in dysregulated genes between EoE‐PPI‐TSnr and EDP, with a perfect agreement in the directionality of modulation. Eosinophils, dendritic cells (DCs), immature DCs, megakaryocytic‐erythroid progenitors, and T helper type 1 cells were significantly higher in EoE‐PPI‐TSnr. There was no significant difference in microbiome diversity. The relative abundance of Fusobacterium sp. and Acinetobacter sp. notably differed in EoE‐PPI‐TSnr and correlated with the key pathways. Conclusion: Our results provide critical insights into the molecular, cellular, and microbial factors associated with the lack of response to PPI and TS combination therapy in children with EoE. This study advances our understanding of the pathobiology of EoE while guiding personalized treatment strategies. [ABSTRACT FROM AUTHOR]

This article examines the connection between elevated wheat IgG4 antibody levels and autism spectrum disorder (ASD) in children. The study discovered that children with ASD and high levels of wheat IgG4 antibodies had changes in their gut microbiota and were more susceptible to certain pathogens. These children also experienced alterations in gut microbial carbohydrate-activating enzymes, which impacted their ability to metabolize dietary fiber. These findings suggest a potential relationship between food hypersensitivities, gut microbiota, and ASD. The document discusses the results of a study on the association between food-specific IgG4 antibodies and intestinal infections in children with ASD. The study found that increased IgG4 levels for foods like wheat, milk, yogurt, sheep milk, and eggs were linked to a higher presence of E. coli in fecal samples. The researchers propose that targeting individuals with high levels of food-specific IgG4 antibodies may be more effective in developing dietary interventions for children with ASD. Further research is planned to investigate the presence of immune complexes in the intestinal mucosa. [Extracted from the article]

Background Methods Results Conclusion Recently, we have identified a dysregulated protein signature in the esophageal epithelium of eosinophilic esophagitis (EoE) patients including proteins associated with inflammation and epithelial barrier function; however, the effect of proton pump inhibitor (PPI) treatment on this signature is unknown. Herein, we used a proteomic approach to investigate: (1) whether PPI treatment alters the esophageal epithelium protein profile observed in EoE patients and (2) whether the protein signature at baseline predicts PPI response.We evaluated the protein signature of esophageal biopsies using a cohort of adult EoE (n = 25) patients and healthy controls (C) (n = 10). In EoE patients, esophageal biopsies were taken before (pre) and after (post) an 8‐week PPI treatment, determining the histologic response. Eosinophil count PostPPI was used to classify the patients: ≥15 eosinophils/hpf as non‐responders (non‐responder) and < 15 eosinophils/hpf as responders (R). Protein signature was determined and differentially accumulated proteins were characterized to identify altered biological processes and signaling pathways.Comparative analysis of differentially accumulated proteins between groups revealed common signatures between three groups of patients with inflammation (responder‐PrePPI, non‐responder‐PrePPI, and non‐responder‐PostPPI) and without inflammation (controls and responder‐PostPPI). PPI therapy almost reversed the EoE specific esophageal protein signature, which is enriched in pathways associated with inflammation and epithelial barrier function, in responder‐PostPPI. Furthermore, we identified a set of candidate proteins to differentiate responder‐PrePPI and non‐responder‐PrePPI EoE patients before treatment.These findings provide evidence that PPI therapy reverses the alterations in esophageal inflammatory and epithelial proteins characterizing EoE, thereby providing new insights into the mechanism of PPI clinical response. Interestingly, our results also suggest that PPI response could be predicted at baseline in EoE. [ABSTRACT FROM AUTHOR]

The epithelial barriers of the skin, gut, and respiratory tract are critical interfaces between the environment and the host, and they orchestrate both homeostatic and pathogenic immune responses. The mechanisms underlying epithelial barrier dysfunction in allergic and inflammatory conditions, such as atopic dermatitis, food allergy, eosinophilic oesophagitis, allergic rhinitis, chronic rhinosinusitis, and asthma, are complex and influenced by the exposome, microbiome, individual genetics, and epigenetics. Here, we review the role of the epithelial barriers of the skin, digestive tract, and airways in maintaining homeostasis, how they influence the occurrence and progression of allergic and inflammatory conditions, how current treatments target the epithelium to improve symptoms of these disorders, and what the unmet needs are in the identification and treatment of epithelial disorders. [ABSTRACT FROM AUTHOR]

A study published in the journal Allergy suggests that salivary immunoinflammatory proteins could be used as a less invasive method for identifying children with eosinophilic esophagitis (EoE). Currently, EoE is diagnosed through invasive procedures. The study collected saliva samples from children with EoE and controls and used proximity extension analysis to analyze the proteins. The findings indicate that a panel of proteins could accurately distinguish children with EoE from controls and differentiate between different subtypes of EoE. This research suggests that salivary proteins have diagnostic potential and could serve as non-invasive biomarkers for EoE, but further research is needed to validate these findings. [Extracted from the article]

This document provides concise summaries of various case reports, research studies, and articles related to different medical conditions, allergies, immune responses, and respiratory diseases. The summaries highlight important findings and insights into the diagnosis, treatment, and management of these conditions. The document covers topics such as chlorhexidine allergies, allergic contact dermatitis, eosinophilic esophagitis, asthma, COVID-19, food allergies, and immune system abnormalities. [Extracted from the article]

This document is a compilation of summaries of various articles published in the journal Allergy. The articles cover a range of topics related to allergies and immunology. Some of the topics include the recognition of epitopes in birch pollen allergic patients, the correlation between blood eosinophils and asthma severity, the role of heat shock protein 10 in chronic spontaneous urticaria, the prevalence of IgE autoantibodies in atopic dermatitis, the co-localization of IgG4 and cow's milk proteins in eosinophilic esophagitis, the comparison of different food challenge methods in peanut allergy, the safe doses of sesame in sesame allergic patients, the immunogenicity of thermostable allergens in canned fish, the food-induced immediate response of the esophagus in pediatric eosinophilic esophagitis, and the potential use of specific IgE as a biomarker in alpha-gal red meat allergy. [Extracted from the article]

Background: Food‐induced immediate response of the esophagus (FIRE) is a new phenomenon that has been described in eosinophilic esophagitis (EoE) patients. It is suspected when unpleasant symptoms occur suddenly on contact of the triggering food with the esophageal surface and recur with repeated exposures. It can often be mistaken for pollen‐food allergy syndrome (PFAS) and solid food dysphagia. Data on FIRE is limited to one survey study and case reports, and there are no screening studies conducted on either adults or children with EoE. In this study, we aimed to screen children aged ≥7 years old with EoE for FIRE. Methods: Demographic data were collected from medical records. A questionnaire about FIRE was applied to all participants. Skin prick tests were done on suspected patients to identify the triggering foods. FIRE is defined as suitable clinical symptoms with suspected food allergen exposure. Results: A total of 78 patients (74.4% male, median age: 13.5 years) were included. Unpleasant and recurrent symptoms distinct from dysphagia with specific foods were reported in 16.7% of the patients, all of whom had concomitant allergic rhinitis (AR). The symptoms described by almost all patients were oropharyngeal itching and tingling (PFAS: 15.3%) excluding only one patient reporting retrosternal narrowing and pressure after specific food consumption (FIRE: 1.2%). Conclusions: Although definitive conclusions regarding the true prevalence of FIRE cannot be made, it does not seem to be common as PFAS. However, it deserves questioning particularly in the presence of concurrent AR and/or PFAS in children with EoE. [ABSTRACT FROM AUTHOR]

Background: Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co‐localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits. Methods: This study included adult subjects with EoE (n = 13) and non‐EoE controls (n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co‐localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4‐food protein interactions were confirmed with co‐immunoprecipitation and mass spectrometry. Results: IgG4‐CMP co‐localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p =.02; Bos d 5, p =.002; Bos d 8, p =.002). Co‐localization was also significantly higher in the active EoE group compared to non‐EoE controls (Bos d 4, p =.0013; Bos d 5, p =.0007; Bos d 8, p =.0013). AutoSTOMP identified eosinophil‐derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain‐14 in IgG4‐enriched areas. Co‐immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens. Conclusion: These findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression. [ABSTRACT FROM AUTHOR]

Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. Duygu Yazici, Eren Cagan, Ge Tan, Manru Li, Evan Do, Ozan C. Kucukkase, Abdurrahman Simsek, Muhammed Ali Kizmaz, Tugce Bozkurt, Tamer Aydin, Anja Heider, Beate Rückert, Marie-Charlotte Brüggen, Raja Dhir, Liam O'Mahony, Mubeccel Akdis, Kari C. Nadeau, Ferah Budak, Cezmi A. Akdis, Ismail Ogulur This study provides evidence that epithelial barrier function is compromised in severe COVID-19, which is also in line with the epithelial barrier theory. We demonstrated certain protein biomarkers with disease progression from moderate to severe COVID-19 and death. [Extracted from the article]

Background: Eosinophilic esophagitis (EoE) is a chronic non‐IgE‐mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq‐based transcriptomic analysis in paired samples was also carried out. Methods: Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE‐specific mRNA panels (EDP and Eso‐EoE panel). Results: A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA‐proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil‐related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso‐EoE, and corresponded with the most abundant proteins of the human esophageal proteome. Conclusions: We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms. [ABSTRACT FROM AUTHOR]

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]

The article discusses the identification of salivary immunoinflammatory proteins that can help diagnose children with eosinophilic esophagitis (EoE). The study found that inflammatory cytokines, including interleukin-17, correlated with the severity of esophageal mucosal involvement, but not with peak eosinophil count. The research suggests that EoE pathophysiology involves more than just eosinophils, highlighting the need for a multidimensional assessment in disease monitoring and management. Additionally, IL-17 may play a role in EoE pathogenesis, but further studies are needed to confirm its utility as a noninvasive biomarker. [Extracted from the article]

Wilcoxon matched-pairs signed rank test: *p < .05, **p < .01. gl In contrast, a less invasive biopsy-based ex vivo food challenge test may be considered a promising tool for the identification of causative foods in EoE patients. Of the in total 17 foods that induced acute responses following local injections, 9 foods (53%) corresponded with patient's clinical history, 6 (35%) with SPT results and 6 (35%) with serum IgE results. Elimination diets without the causative foods induce histological and clinical remission in patients with eosinophilic esophagitis (EoE), an allergen-driven type 2 inflammatory disease of the esophagus.[1] However, current tests using skin or serum are poorly predictive of the causative foods,[2] likely because the allergic inflammation may be restricted to the esophagus. [Extracted from the article]

Background: Eosinophilic esophagitis (EoE) is a chronic, food‐driven allergic disease, characterized by eosinophil‐rich inflammation in the esophagus. The histopathological and clinical features of EoE have been attributed to overproduction of the type 2 cytokines IL‐4 and IL‐13, which mediate profound alterations in the esophageal epithelium and neutralizing of their shared receptor component (IL‐4Rα) with a human antibody drug (dupilumab) demonstrates clinical efficacy. Yet, the relative contribution of IL‐4 and IL‐13 and whether the type II IL‐4 receptor (comprised of the IL‐4Rα chain in association with IL‐13Rα1) mediates this effect has not been determined. Methods: Experimental EoE was induced in WT, Il13ra1−/−, and Krt14Cre/Il13ra1fl/fl mice by skin‐sensitized using 4‐ethoxymethylene‐2‐phenyl‐2‐oxazolin (OXA) followed by intraesophageal challenges. Esophageal histopathology was determined histologically. RNA was extracted and sequenced for transcriptome analysis and compared with human EoE RNAseq data. Results: Induction of experimental EoE in mice lacking Il13ra1 and in vivo IL‐13 antibody‐based neutralization experiments blocked antigen‐induced esophageal epithelial and lamina propria thickening, basal cell proliferation, eosinophilia, and tissue remodeling. In vivo targeted deletion of Il13ra1 in esophageal epithelial cells rendered mice protected from experimental EoE. Single‐cell RNA sequencing analysis of human EoE biopsies revealed predominant expression of IL‐13Rα1 in epithelial cells and that EoE signature genes correlated with IL‐13 expression compared with IL‐4. Conclusions: We demonstrate a definitive role for IL‐13 signaling via IL‐13Rα1 in EoE. These data provide mechanistic insights into the mode of action of current therapies in EoE and highlight the type II IL‐4R as a future therapeutic target. [ABSTRACT FROM AUTHOR]

Given the limited clinical effect of eosinophil-directed therapies in EoE to date, our data support exploring the clinical benefit of anti-MC agents in EoE. Pearson correlations performed with MC-specific protease carboxypeptidase A3 ( I CPA3 i ) demonstrated a strong correlation with eosinophil transcriptional signatures, including the eotaxin receptor I CCR3 i , the eosinophil granule lysophospholipase ( I CLC i ), and the eosinophil chemokines eotaxin-3 ( I CCL26 i ) and I IL5 i (Figures 1 and 2A). Abbreviations EoE eosinophilic esophagitis EDP eosinophilic esophagitis diagnostic panel MC mast cell PEC peak eosinophil count Eosinophilic esophagitis (EoE) is a type 2 inflammatory disorder characterized by esophageal inflammation, eosinophil infiltration, tissue remodeling, and stricture.[1] Currently, diagnosis of EoE is based on clinical assessments and a peak tissue eosinophil count (PEC) of >=15 eosinophils per high powered field, although PEC does not correlate well with symptom severity, and eosinophil reduction to normal levels does not correlate with symptomatic improvement in some studies.[1] Numerous studies have demonstrated that mast cells (MCs) are also present in significantly greater numbers in EoE than in normal esophageal biopsies. [Extracted from the article]

As seen, expression of non-fs EoE is intermediate between FS-EoE and controls in these examples regardless if statistically different between FS-EoE and non-fs EoE or not. Approximately 90% of the DEGs identified between FS-EoE versus control follow a pattern in which non-fs EoE has expression intermediate between controls and FS EoE. Eosinophilic Esophagitis (EoE) is a chronic inflammatory esophageal disease in which a subset of patients undergo pathologic tissue remodeling. [Extracted from the article]

Acute and baseline serum samples were obtained from 150 patients with hypersensitivity reactions. Derived CCD-specific IgE detect CCD-carrying allergens and are capable of mediating effector cell activation and facilitated allergen binding. MA and a logistic regression model was fitted (AUC = 0.896). miR-21-5p and miR-126-3p increased in T2high-Atopic asthma, whereas miR-21-5p, miR-126-3p, and miR-146a-5p levels were downregulated in IL-6high MSA patients. [Extracted from the article]

Background: Eosinophilic esophagitis (EoE) is a chronic allergic disease associated with type 2 inflammation and epithelial barrier dysfunction. The etiology is unknown, however, genetic heritability studies suggest environmental factors play a key role in pathogenesis. Detergents, such as sodium dodecyl sulfate (SDS), are common ingredients in household products such as dish soap and toothpaste. We hypothesized detergent exposure decreases epithelial barrier function and induces esophageal inflammation. Methods: Immortalized esophageal epithelial cells (EPC2) were cultured in air‐liquid interface (ALI) and exposed to SDS. Barrier function/activity was assessed by transepithelial electrical resistance (TEER), FITC‐dextran flux, and RT‐PCR. Additionally, SDS‐treated mouse esophageal organoids were evaluated for morphology. To investigate the effects of SDS in vivo, mice were treated with 0.5% SDS in drinking water for 14 days. Esophagi were assessed by gross morphology, histopathology, protein expression, and bulk RNA sequencing. Results: When EPC2 cells were exposed to SDS (5 μg/ml) for 96 h, TEER decreased (p = 0.03), and FITC‐dextran flux increased (p = 0.0002). mRNA expression of IL‐33 increased 4.5‐fold (p = 0.02) at 6 h and DSG1 decreased (p < 0.0001) by 72 h. Disrupted epithelial integrity was noted in SDS‐treated esophageal organoids. When mice were exposed to SDS, they showed increased esophageal width, chemokine, and metalloprotease levels. Mice treated with SDS also showed increased IL‐33 protein expression, basal zone hyperplasia, CD4+ cell infiltration, and esophageal eosinophilia. RNA sequencing revealed upregulation of immune response pathway genes. Conclusion: Exposure to SDS decreases esophageal barrier integrity, stimulates IL‐33 production, and promotes epithelial hyperplasia and tissue eosinophilia. Detergents may be a key environmental trigger in EoE pathogenesis. [ABSTRACT FROM AUTHOR]

Laundry detergents and detergent residue after rinsing directly disrupt tight junction barrier integrity in human bronchial epithelial cells. Keywords: detergent; eosinophilic inflammation; epithelial barrier theory; SDS EN detergent eosinophilic inflammation epithelial barrier theory SDS 1422 1424 3 06/02/23 20230601 NES 230601 Since the 1960s, there has been an increasing prevalence of allergic, autoimmune, and metabolic diseases. Tissue eosinophilia, inflammation, abscess formation, CD4+ T cell infiltration, and remodeling are observed. [Extracted from the article]

Moritz M. Hollstein, Lennart Münsterkötter, Michael P. Schön, Armin Bergmann, Thea M. Husar, Anna Abratis, Abass Eidizadeh, Meike Schaffrinski, Karolin Zachmann, Anne Schmitz, Jason S. Holsapple, Hedwig Stanisz-Bogeski, Julie Schanz, Andreas Fischer, UWE GROß, Andreas Leha, Andreas E. Zautner, Moritz Schnelle, Luise Erpenbeck Booster with BNT162b2 elicits strong humoral and cellular immune responses independent of the prime vaccination, whereas ChAdOx1 nCoV-19 booster does not further enhance the cellular response. We demonstrate that the vaccine candidate (CuMV SB TT sb -RBD) is highly immunogenic in mice and is capable of inducing mucosal and systemic RBD as well as spike specific antibody responses. GRAPH Abbreviations: CDX-0159, anti-KIT inhibitory monoclonal antibody; FcR, Fc receptor; KIT, KIT proto-oncogene, receptor tyrosine kinase; MRGPRX2, mas-related G protein-coupled receptor-X2; SCF, stem cell factor. [Extracted from the article]

Objective: Physicians are increasingly confronted with patients presenting with symptoms of esophageal dysfunction resembling eosinophilic esophagitis (EoE), but absence of significant esophageal eosinophilia. The purpose of this study was to characterize and classify this group of EoE variants. Design: Patients from six EoE‐centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <60/mm2 (<15/hpf) in esophageal biopsies and absence of gastro‐esophageal reflux disease (GERD) were included. Clinical, endoscopic, (immuno)‐histological, and molecular features were determined and compared with EoE, GERD, and healthy controls. Results: We included 69 patients with EoE variants. Endoscopic abnormalities were found in 53.6%. We identified three histological subtypes: EoE‐like esophagitis (36/69, 52.2%), lymphocytic esophagitis (14/69, 20.3%), and non‐specific esophagitis (19/69, 27.5%). Immunohistochemistry revealed—in contrast to EoE—no significant increase in inflammatory cell infiltrates compared with GERD and healthy controls, except for lymphocytes in lymphocytic esophagitis. EoE‐typical Th2‐response was absent in all EoE variants. However, considerable structural changes were detected based on histology and protein expression. Using next generation mRNA sequencing, we found the three EoE variants to have distinct molecular fingerprints partially sharing pronounced traits of EoE. Hierarchical sample clustering of RNA sequencing data confirmed the presence of an EoE‐like (characterized by eotaxin‐3 expression), non‐specific, and lymphocytic variant cluster (characterized by CD3 cells and TSLP expression). Conclusion: All EoE variants are clinically and histologically active conditions despite the absence of esophageal eosinophilia. EoE variants appear to be part of a disease spectrum, where classical EoE represents the most common and apparent phenotype. [ABSTRACT FROM AUTHOR]

Abbreviations CCHMC Cincinnati Children's Hospital Medical Center CEGIR Consortium of Eosinophilic Gastrointestinal Disease Researchers EDP eosinophilic esophagitis diagnostic panel EoE eosinophilic esophagitis HPF high-power field MC Mast cells; PRO, Patient-reported outcome EEsAI eosinophilic esophagitis activity index PEESS Pediatric Eosinophilic Esophagitis Symptom Scores HSS EoE Histology Scoring System EREFS EoE endoscopic reference score CONFLICT OF INTEREST M.E.R. is a consultant for Pulm One, Spoon Guru, Allakos, ClostraBio, Serpin Pharm, Celgene, Shire, AstraZeneca, GlaxoSmithKline, Allakos, Adare, Regeneron, and Novartis and has an equity interest in the first five, as well as royalties from reslizumab (Teva Pharmaceuticals) and UpToDate. Mast cells (MCs) are involved in allergy, including EoE,2 and neuromodulation.3 MCs reside in peripheral tissue and communicate with nearby structures, including nerve endings. We divided active EoE into four quartiles by using I CPA3 i + I HPGDS i sum as a MC count surrogate marker; the highest and lowest quartiles represented MC-high and MC-low, respectively. [Extracted from the article]

Background: Eosinophilic esophagitis (EoE) is a food allergen driven disease that is accompanied by interleukin (IL) 13 overexpression and esophageal barrier dysfunction allowing transepithelial food allergen permeation. Nutraceuticals, such as short‐chain fatty acids (SCFAs) that restore barrier function and increase immune fitness may be a promising tool in the management of EoE. Here, we investigated the effects of the SCFAs acetate, propionate, and butyrate on an IL‐13‐compromised human esophageal epithelial barrier, including the mechanisms involved. Methods: An air‐liquid interface culture model of differentiated human EPC2‐hTERT (EPC2) was used to study whether SCFAs could restore barrier function after IL‐13‐induced impairment. Esophageal epithelial barrier function was monitored by transepithelial electrical resistance (TEER) and FITC‐dextran paracellular flux, and was further examined by qPCR and immunohistochemical analysis. G protein‐coupled receptor (GPR) GPR41, GPR43, GPR109a, or histone deacetylase (HDAC) (ant)agonists were used to assess mechanisms of action of SCFAs. Results: IL‐13 stimulation decreased TEER and increased FITC flux, which was counteracted by butyrate and propionate, but not acetate treatment. Barrier proteins FLG and DSG1 mRNA expression was upregulated following butyrate and propionate treatment, whereas expression of eosinophil chemoattractant CCL26 and protease CAPN14 was downregulated. Similarly, butyrate and propionate restored FLG and DSG1 protein expression. Similar effects were observed with an HDAC antagonist but not with GPR agonists. Conclusion: Nutraceuticals butyrate and propionate restore the barrier function of esophageal epithelial cells after an inflammatory insult and may be of therapeutic benefit in the management of EoE. [ABSTRACT FROM AUTHOR]

Environmental exposure plays a major role in the development of allergic diseases. The exposome can be classified into internal (e.g., aging, hormones, and metabolic processes), specific external (e.g., chemical pollutants or lifestyle factors), and general external (e.g., broader socioeconomic and psychological contexts) domains, all of which are interrelated. All the factors we are exposed to, from the moment of conception to death, are part of the external exposome. Several hundreds of thousands of new chemicals have been introduced in modern life without our having a full understanding of their toxic health effects and ways to mitigate these effects. Climate change, air pollution, microplastics, tobacco smoke, changes and loss of biodiversity, alterations in dietary habits, and the microbiome due to modernization, urbanization, and globalization constitute our surrounding environment and external exposome. Some of these factors disrupt the epithelial barriers of the skin and mucosal surfaces, and these disruptions have been linked in the last few decades to the increasing prevalence and severity of allergic and inflammatory diseases such as atopic dermatitis, food allergy, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis, and asthma. The epithelial barrier hypothesis provides a mechanistic explanation of how these factors can explain the rapid increase in allergic and autoimmune diseases. In this review, we discuss factors affecting the planet's health in the context of the 'epithelial barrier hypothesis,' including climate change, pollution, changes and loss of biodiversity, and emphasize the changes in the external exposome in the last few decades and their effects on allergic diseases. In addition, the roles of increased dietary fatty acid consumption and environmental substances (detergents, airborne pollen, ozone, microplastics, nanoparticles, and tobacco) affecting epithelial barriers are discussed. Considering the emerging data from recent studies, we suggest stringent governmental regulations, global policy adjustments, patient education, and the establishment of individualized control measures to mitigate environmental threats and decrease allergic disease. [ABSTRACT FROM AUTHOR]

Background: Food allergen immunotherapy (FA‐AIT) practice is known to vary globally. This project aims to identify and characterize European centres performing FA‐AIT. Methods: An EAACI task force conducted an online survey to gather relevant information regarding FA‐AIT practice and setting‐specific resources after reviewing the published literature and congress abstracts throughout Europe. Results: We identified 102 FA‐AIT centres in 18 countries; only Spain (n = 39) and France (n = 16) had ≥10 such centres. Overall, most facilities were hospital‐based (77.5%), publicly funded (80.4%) and delivered FA‐AIT as routine clinical care (80.4%). On average, departments had 3 allergists/paediatric allergists and 2 nurses. Surveyed centres had provided FA‐AIT for a median of 9 years [1–24] to a median of 105 [5–2415] patients. The estimated total number of treated patients was 24875, of whom 41.3% received AIT for milk, 34.2% egg, 12.8% peanut and 11.7% other foods. Anaphylaxis to AIT doses requiring over 4–6 h of observation was reported by 70.6% of centres, ICU admissions by 10.8% and eosinophilic esophagitis by 45.1%. Quality of life and sustained unresponsiveness were evaluated in 20.6% and 54.9% of centres, respectively. The main contraindications for food AIT were severe asthma (57%‐63%), eosinophilic esophagitis (56%‐48%) and age below 5 years (47%‐41%). Conclusions: In Europe, FA‐AIT is provided mostly in clinical practice. Significant variation is seen in the number of centres per country, facility characteristics and inclusion/exclusion criteria, and in certain aspects of protocols. Potential inequality in access to AIT has been identified as well as the need for education and guidance for treatment standardization. [ABSTRACT FROM AUTHOR]

RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: two unique cell fates and CD29 as a biomarker for treatment effect. Single-cell RNA sequencing can profile the transcriptome of individual cells, thus enabling the unbiased characterization of mixed populations of cells to identify novel cellular populations. The immune system is a highly interactive networking of more than 30 actively migrating cells with resident tissue cells, which makes its decisions based on input from all organs and tissues, infections, normal flora bacteria, and many or even any environmental agents. [Extracted from the article]

Tissue eosinophils express the IL-33 receptor ST2 and type 2 cytokines in patients with eosinophilic esophagitis Keywords: clinical immunology; eosinophils; flow cytometry; interleukins; mucosal immunity EN clinical immunology eosinophils flow cytometry interleukins mucosal immunity 656 660 5 02/01/22 20220201 NES 220201 ACKNOWLEDGMENTS We would like to acknowledge the contributions from the Harvard Stem Cell Institute-Center for Regenerative Medicine Flow Cytometry Core and the Program for Membrane Biology Microscopy Core at Simches Research Center, Massachusetts General Hospital. ST2 was robustly detected on tissue eosinophils from patients with active EoE (Figure 1C, 1E), whereas blood eosinophils from healthy control, remission, and active EoE were uniformly low for ST2 (Figure 1D, 1F-G; Figure S1). [Extracted from the article]

Background: Esophageal histology is critical for diagnosis and surveillance of disease activity in eosinophilic esophagitis (EoE). A validated noninvasive biomarker has not been identified. We aimed to determine the utility of blood and urine eosinophil‐associated proteins to diagnose EoE and predict esophageal eosinophilia. Methods: Blood and urine were collected from children undergoing endoscopy with biopsy. Absolute eosinophil count (AEC), plasma eosinophil‐derived neurotoxin (EDN), eosinophil cationic protein (ECP), major basic protein‐1 (MBP‐1), galectin‐10 (CLC/GAL‐10), Eotaxin‐2 and Eotaxin‐3, and urine osteopontin (OPN) and matrix metalloproteinase‐9 (MMP‐9) were determined. Differences were assessed between EoE and control, and with treatment response. The capacity to predict EoE diagnosis and esophageal eosinophil counts was assessed. Results: Of 183 specimens were collected from 56 EoE patients and 15 non‐EoE controls with symptoms of esophageal dysfunction; 33 EoE patients had paired pre‐ and post‐treatment specimens. Plasma (CLC/GAL‐10, ECP, EDN, Eotaxin‐3, MBP‐1) and urine (OPN) biomarkers were increased in EoE compared to control. A panel comprising CLC/GAL‐10, Eotaxin‐3, ECP, EDN, MBP‐1, and AEC was superior to AEC alone in distinguishing EoE from control. AEC, CLC/GAL‐10, ECP, and MBP‐1 were significantly decreased in patients with esophageal eosinophil counts <15/hpf in response to treatment. AEC, CLC/GAL‐10, ECP, EDN, OPN, and MBP‐1 each predicted esophageal eosinophil counts utilizing mixed models controlled for age, gender, treatment, and atopy; AEC combined with MBP‐1 best predicted the counts. Conclusions: We identified novel panels of eosinophil‐associated proteins that along with AEC are superior to AEC alone in distinguishing EoE from controls and predicting esophageal eosinophil counts. [ABSTRACT FROM AUTHOR]

Background: Eosinophilic esophagitis (EoE) is a T‐cell‐mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE‐causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen‐specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE. Methods: We obtained blood samples from control subjects (n = 17), subjects with clinical EoE milk allergy (n = 17), and subjects with immunoglobulin E‐mediated milk allergy (n = 9). We measured total and milk‐specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4+ T helper (TH) cell proliferation and cytokine production after stimulation with endotoxin‐depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches. Results: Total and milk‐specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused TH lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p < 0.0001), and produce more type 2 cytokines (%IL‐4+ of 33.7 ± 2.8 vs. 6.9 ± 1.6, p < 0.0001) than cells from control subjects. Milk‐dependent memory TH‐cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL‐4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy. Conclusions: Peripheral markers of allergen‐specific immune activation may be useful in identifying EoE‐causal foods. Assaying milk‐dependent IL‐4 production by circulating memory TH lymphocytes most accurately predicts clinical EoE milk allergy. [ABSTRACT FROM AUTHOR]

Background: Eosinophils are specialized granulocytic effector cells that store and release highly active mediators used in immune defense. Eosinophils are also implicated in the pathogenesis of allergic disorders, including eosinophilic esophagitis (EoE), a chronic disorder characterized by infiltration of eosinophils into the esophagus and release of mediators that damage tissue, resulting in gastrointestinal morbidity, food impaction, and dysphagia. Treatment with elimination diets and/or topical corticosteroid therapy slow disease progression, but are complicated by adverse effects, limited compliance, and loss of response to therapy. We hypothesized that a single administration of an adeno‐associated virus (AAV) coding for an anti‐eosinophil monoclonal antibody that induces eosinophil clearance (anti‐Siglec‐F) would treat on a persistent basis a murine model of EoE. Methods: A mouse model of peanut‐induced EoE that mimics the human disease was established by sensitization and challenge with peanut extract. After challenge, these mice exhibited an EoE phenotype demonstrated by elevated levels of blood eosinophils, infiltration of eosinophils in the esophagus with associated esophageal remodeling and food impaction. Results: The mice were treated with a single intravenous administration (1011 genome copies) of AAVrh.10mAnti‐Eos, a serotype rh.10 AAV vector coding for an anti‐Siglec‐F monoclonal antibody. Vector administration resulted in persistent, high levels of anti‐Siglec‐F antibody expression. Administration of AAVrh.10mAnti‐Eos to the mouse model of EoE reduced blood (P < 0.02) and esophageal eosinophil numbers (P < 0.002) protected from esophageal tissue remodeling and minimized food impaction. Conclusion: These results suggest that a single treatment with AAVrh.10mAnti‐Eos has the potential to provide persistent therapeutic benefit to patients with EoE. [ABSTRACT FROM AUTHOR]

Keywords: eosinophils; esophagitis; food allergy; milk food allergy; epicutaneous immunotherapy EN eosinophils esophagitis food allergy milk food allergy epicutaneous immunotherapy 1573 1576 4 05/17/21 20210501 NES 210501 Eosinophilic esophagitis (EoE) is an allergic disease of the esophagus without any curative therapy. After CM-induced EoE was confirmed, EPIT was applied daily for 9 months during a CM-free period, followed by CM-containing diet for 2 months. Eosinophils, esophagitis, food allergy, milk food allergy, epicutaneous immunotherapy. [Extracted from the article]

Characterization of the esophageal microbiota in EoE subjects relative to non-EoE controls was performed by comparison of steroid-naïve subjects with active or inactive EoE to non-EoE controls. We aimed to characterize the bacterial and fungal communities in the esophageal mucosa of children with EoE and non-EoE controls and examine the effects of TSS on the microbiota in children with EoE. Eosinophilic esophagitis (EoE) is a chronic inflammatory disease characterized by an eosinophil-predominant inflammation of the esophageal mucosa.1 We have previously characterized bacterial communities of the human esophagus in healthy children and adults.2 Our data and work from others suggest that the normal esophageal bacterial microbiota is dominated by I Firmicutes i species.2-4 Active inflammation in EoE is associated with bacterial dysbiosis, specifically with an increase in members of the I Proteobacteria i .2,3 However, while some have described the role of bacteria in atopic gastrointestinal diseases,5 little is known about the role of fungi in allergic esophageal inflammation or the role of topical swallowed steroids (TSS) in disease-associated dysbiosis. [Extracted from the article]

This ETR replaces the requirements for training in Allergology and Clinical Immunology as defined in Chapter 6 of the UEMS Charter on Training of Medical Specialist in the EU (2003). The complete version of the ETR can be found on the UEMS website.2 This ETR focuses on Allergology, since at European level our specialty has been recognized only as Allergology. To the Editor, The development of the European training requirements (ETR) for medical specialties in Europe is regulated by the Union Europeénne des Médecins Spécialistes (UEMS), a non-governmental organization representing national associations of medical specialists at European Level. [Extracted from the article]

Keywords: eosinophilic enteritis; eosinophilic gastritis; eosinophilic gastrointestinal disease; GATA-3; pediatric subjects; T-bet EN eosinophilic enteritis eosinophilic gastritis eosinophilic gastrointestinal disease GATA-3 pediatric subjects T-bet 1042 1044 3 03/02/22 20220301 NES 220301 ACKNOWLEDGEMENTS The study was funded by Mayo Clinic, Phoenix Children's Hospital Foundation, and the Donald R. Levin Family Foundation. We recently examined T-bet and GATA-3 expression in biopsies from pediatric subjects with EoE, proton pump inhibitor-responsive EoE, and controls and found that both T-bet and GATA-3 expression were increased in EoE subjects.3 This study expands on our initial findings by examining these nuclear transcription factors in subjects with eosinophilic gastritis and/or duodenitis. Slides were digitized and analyzed as previously described.3 Percentages of T-bet+and GATA-3+ nuclei were correlated to tissue eosinophil counts and compared between EG/EoD cases and controls. [Extracted from the article]

Severe asthma patients with ACO used more systemic corticosteroids and had more frequent exacerbations related to emergency department visits than those without ACO. Dupilumab reduces severe exacerbations and improves lung function and asthma control in patients on high-dose ICS with elevated baseline blood eosinophils or FeNO. Patients with asthma exacerbations have a higher % of Th2 cells (CD4 SP + sp T cells expressing CRTh2) in peripheral blood compared to patients with stable asthma, and this parameter decreases after treatment. [Extracted from the article]

Background: Dysphagia is the main symptom of adult eosinophilic esophagitis (EoE). We describe a novel syndrome, referred to as "food‐induced immediate response of the esophagus" (FIRE), observed in EoE patients. Methods: Food‐induced immediate response of the esophagus is an unpleasant/painful sensation, unrelated to dysphagia, occurring immediately after esophageal contact with specific foods. Eosinophilic esophagitis experts were surveyed to estimate the prevalence of FIRE, characterize symptoms, and identify food triggers. We also surveyed a large group of EoE patients enrolled in the Swiss EoE Cohort Study for FIRE. Results: Response rates were 82% (47/57) for the expert and 65% (239/368) for the patient survey, respectively. Almost, 90% of EoE experts had observed the FIRE symptom complex in their patients. Forty percent of EoE patients reported experiencing FIRE, more commonly in patients who developed EoE symptoms at a younger age (mean age of 46.4 years vs 54.1 years without FIRE; P <.01) and in those with high allergic comorbidity. Food‐induced immediate response of the esophagus symptoms included narrowing, burning, choking, and pressure in the esophagus appearing within 5 minutes of ingesting a provoking food that lasted less than 2 hours. Symptom severity rated a median 7 points on a visual analogue scale from 1 to 10. Fresh fruits/vegetables and wine were the most frequent triggers. Endoscopic food removal was significantly more commonly reported in male patients with vs without FIRE (44.3% vs 27.6%; P =.03). Conclusions: Food‐induced immediate response of the esophagus is a novel syndrome frequently reported in EoE patients, characterized by an intense, unpleasant/painful sensation occurring rapidly and reproducibly in 40% of surveyed EoE patients after esophageal contact with specific foods. [ABSTRACT FROM AUTHOR]

Keywords: asthma; atopic dermatitis; bioinformatics; food allergy; "omics" and systems biology EN asthma atopic dermatitis bioinformatics food allergy "omics" and systems biology 1789 1793 5 07/14/20 20200701 NES 200701 Driven mostly by the recent explosion of high-throughput technologies including sequencing, genotyping, and big data analytics, a vast amount of multi-omics and functional annotation data are accumulating for allergic diseases. GLO:1X5/01jul20:all14219-fig-0002.jpg PHOTO (COLOR): Gene word cloud summary of the five major allergic diseases (asthma, atopic dermatitis, food allergy, allergic rhinitis, and eosinophilic esophagitis). Food allergy and eosinophilic esophagitis share 100% genes with asthma, while atopic dermatitis and allergic rhinitis share 88.7% (780/879) and 77.7% (923/1188) of genes with asthma. [Extracted from the article]

Keywords: epidemiology; food allergy; food protein-induced enterocolitis syndrome; FPIES; prevalence EN epidemiology food allergy food protein-induced enterocolitis syndrome FPIES prevalence 1466 1469 4 06/01/20 20200601 NES 200601 Abbreviations FA food allergy FPIES food protein-induced enterocolitis syndrome Eosinophilic esophagitis (EoE) is an atopic disease characterized by eosinophilic inflammation in the esophagus,[1] with the highest disease burden in Western industrialized countries.[2] However, prevalence estimates differ substantially between studies, ranging from as low as 2.3/100 000 in Denmark to as high as 90.7/100 000 in part of the United States.[2] The aforementioned prevalence studies are based on electronic medical records or pathology reports, health insurance claims, patients referred to third level healthcare systems, or subspecialty physician-administered questionnaires;[3] therefore, they tend to reflect specific population prevalence, with consequent potential for socioeconomic and comorbidity selection biases.[2] To the best of our knowledge, no US population-based EoE prevalence estimates have been previously reported. However, the fact that incidence of EoE and its comorbidity is similar to what reported before suggest that this survey-based approach may have captured a population carrying a real EoE diagnosis. Epidemiology, food allergy, food protein-induced enterocolitis syndrome, FPIES, prevalence. [Extracted from the article]

Eosinophilic esophagitis (EoE) is a chronic-inflammatory disease of the esophagus, defined I clinically i by the presence of symptoms of esophageal dysfunction and I histologically i by an eosinophil predominant infiltration in the esophageal mucosa.[1] Due to its chronicity, EoE requires both short-term and long-term treatments.[2] Therapeutic goals are (a) to control clinical activity (resolution of symptoms); and (b) to control biological activity to avoid stricture formation and bolus impaction, a potentially life-threatening event. Treatment of EoE consists of the 3 D's: Drugs, Diet, and Dilation.[2] Dilation should be seen as an add-on treatment since it does not affect underlying inflammation (Figure). Most importantly, any therapy should be maintained as cessation of treatment results in an EoE relapse within only few months.[11] If histological response is not achieved, we recommend switching from PPI ("PPI non-response") or elimination diet to STC. [Extracted from the article]

It is well‐established that food proteins, such as egg, soya, cow's milk and wheat, are detectable in breastmilk for many hours or days after ingestion. Exposure to these proteins is important to the process of developing tolerance but can also sometimes elicit IgE‐mediated and non–IgE‐mediated allergic symptoms in breastfed infants. Non–IgE‐mediated allergy, outside of food protein‐induced allergic proctocolitis and eosinophilic oesophagitis, is not well understood, leading to variations in the diagnosis and management thereof. A primary objective of the European Academy for Allergy and Clinical Immunology is to support breastfeeding in all infants, including those with food allergies. A Task Force was established, to explore the clinical spectrum of non–IgE‐mediated allergies, and part of its objectives was to establish diagnosis and management of non–IgE‐mediated allergies in breastfed infants. Eight questions were formulated using the Patient, Intervention, Comparison, Outcome (PICO) system and Scottish Intercollegiate Guideline Network (SIGN) criteria for data inclusion, and consensus was achieved on practice points through the Delphi method. This publication aims to provide a comprehensive overview on this topic with practice points for healthcare professionals. [ABSTRACT FROM AUTHOR]

Background: Germline‐encoded innate immune pattern recognition receptors (PRR) are expressed at epithelial surfaces and modulate epithelial defenses. Evidence suggests that stimulation of the Toll‐like receptor (TLR) family of PRR may regulate epithelial barrier integrity by upregulating tight junction (TJ) complex protein expression, but it is not known whether this mechanism is utilized in esophageal epithelial cells. TJ complex proteins maintain intact barrier function and are dysregulated in atopic disorders including eosinophilic esophagitis. Methods: Pattern recognition receptors expression was assessed in EoE and control primary esophageal epithelial cells, demonstrating robust expression of TLR2 and TLR3. The three‐dimensional air‐liquid interface culture (ALI) model was used to test whether TLR2 or TLR3 stimulation alters epithelial barrier function using an in vitro model of human epithelium. Transepithelial electrical resistance (TEER) and FITC‐Dextran permeability were evaluated to assess membrane permeability. ALI cultures were evaluated by histology, immunohistochemistry, Western blotting, and chromatin immunoprecipitation (ChIP). Results: TLR3 stimulation did not change TEER in the ALI model. TLR2 stimulation increased TEER (1.28‐ to 1.31‐fold) and decreased paracellular permeability to FITC‐Dextran, and this effect was abolished by treatment with anti‐TLR2 blocking antibody. TJ complex proteins claudin‐1 and zonula occludens‐1 were upregulated following TLR2 stimulation, and ChIP assay demonstrated altered histone 4 acetyl binding at the TJP1 enhancer and CLDN1 enhancer and promoter following zymosan treatment, implying the occurrence of durable chromatin changes. Conclusions: Our findings implicate the TLR2 pathway as a potential regulator of esophageal epithelial barrier function and suggest that downstream chromatin modifications are associated with this effect. [ABSTRACT FROM AUTHOR]

Herein, we describe a series of patients with biopsy-proven eosinophilic esophagitis who identify characteristic symptoms of FIRE following a specific food ingestion. However, the strong association with atopy, the rapid onset of symptoms, and symptoms distinct from dysphagia suggest a local possibly immunologic factor causing an immediate esophageal mucosal response. Recently, a phenomenon with a different symptom referred to as FIRE (food-induced immediate response in the esophagus) has been described in adults with EoE.2 Patients with eosinophilic esophagitis describe these esophageal symptoms as clearly distinct from dysphagia. [Extracted from the article]

Eosinophilic esophagitis (EoE) is a chronic allergic inflammatory disorder, almost always related to food antigens, in which isolated mucosal esophageal infiltration of eosinophils, mast cells, and basophils leads to esophageal dysfunction.[[1]] The goal of this brief review is to discuss a potential diagnosis and treatment options in pediatrics. GLO:1X5/01jun20:all14188-fig-0001.jpg PHOTO (COLOR): Diagnostic algorithm for diagnosis of eosinophilic esophagitis* gl Once the diagnosis of EoE is established, there are two main therapeutic approaches: dietary therapy or swallowed topical steroids (biologic therapy may be available in the future; Figure). Because EoE is not only a chronic disease but also a disease where clinical symptoms do not always correlate with histologic findings, whenever a therapy is started or changed, an endoscopy with biopsy must be performed approximately 3-4 months later. [Extracted from the article]

Abstract: Background: Recent data associate eosinophilic esophagitis (EoE) with IgG4 rather than IgE, but its significance and function have not been determined. Our aims were to measure esophageal IgG4 levels and to determine functional correlations as assessed by histologic and transcriptome analyses. Methods: This case‐control study included pediatric subjects with EoE (≥15 eosinophils/HPF) and non‐EoE controls. Protein lysates were analyzed for IgA, IgM, and IgG1‐IgG4 using the Luminex 100 system; IgE was quantified by ELISA. Esophageal biopsies were scored using the EoE histology scoring system. Transcripts were probed by the EoE diagnostic panel, designed to examine the expression of 96 esophageal transcripts. Results: Esophageal IgG subclasses, IgA, and IgM, but not IgE, were increased in subjects with EoE relative to controls. The greatest change between groups was seen in IgG4 (4.2 mg/g protein [interquartile range: 1.0‐13.1 mg/g protein] vs 0.2 mg/g protein [0.1‐0.9]; P < .0001). Tissue IgG4 levels correlated with esophageal eosinophil counts (P = .0006); histologic grade (P = .0011) and stage (P = .0112) scores; and IL4, IL10, IL13, but not TGFB1, expression and had strong associations with a subset of the EoE transcriptome. Esophageal IgG4 transcript expression was increased and correlated with IgG4 protein levels and IL10 expression. Conclusion: These findings extend prior studies on IgG4 in adult EoE to the pediatric population and provide deeper understanding of the potential significance and regulation of IgG4, demonstrating that IgG4 is a relevant feature of the disease; is closely related to esophageal eosinophil levels, type 2 immunity and T regulatory cytokines; and is likely produced locally. [ABSTRACT FROM AUTHOR]

Background Eosinophilic esophagitis (EoE) is a chronic, immune/antigen-mediated disease characterized by symptoms related to esophageal dysfunction and an eosinophil-predominant inflammation. This study has aimed to investigate whether the recently observed sensitization to Candida albicans in patients with EoE is owing to pre-existing disease and its underlying abnormal epithelial barrier or, alternatively, is linked to corticosteroid ( CS) therapy. Methods Medical histories, as well as serum and tissue samples of 60 patients with EoE (15 CS naive, 45 with current or previous CS therapy) and 20 controls, stored in the Swiss Eosinophilic Esophagitis Database ( SEED) and Biobank, were analyzed. We applied Immuno CAP to measure IgE levels and immunofluorescence techniques to examine epithelial barrier components. Results Patients with EoE had higher total IgE levels and were more frequently sensitized to C. albicans than controls. In EoE tissue specimens, increased numbers of eosinophils and mast cells, a higher expression levels of thymic stromal lymphopoietin ( TSLP), cathelicidin, proteases, that is, the kallikreins ( KLK)-5 and KLK-7, were observed as compared with controls, while reduced expression of lympho-epithelial Kazal-type-related inhibitor ( LEKTI), filaggrin, E-cadherin, claudin, occludin, desmoglein-1 was found, independent of CS therapy. In CS-treated EoE, significantly lower numbers of CD1a+ cells and cathelicidin expression were noted as compared to CS-naive EoE. Conclusion This study provides further evidence that EoE is associated with an abnormal epithelial barrier and postulates that CS therapy, by reducing innate immune mechanisms, may promote C. albicans colonization and likely subsequent sensitization. [ABSTRACT FROM AUTHOR]