Browsing by Author "Yang, Guang-Yu"
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Item Creating a multi-center rare disease consortium - the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)(IOS Press, 2017-12-18) Cheng, Katherine; Gupta, Sandeep K.; Kantor, Susanna; Kuhl, Jonathan T.; Aceves, Seema S.; Bonis, Peter A.; Capocelli, Kelley E.; Carpenter, Christina; Chehade, Mirna; Collins, Margaret H.; Dellon, Evan S.; Falk, Gary W.; Gopal-Srivastava, Rashmi; Gonsalves, Nirmala; Hirano, Ikuo; King, Eileen C.; Leung, John; Krischer, Jeffrey P.; Mukkada, Vincent A.; Schoepfer, Alain; Spergel, Jonathan M.; Straumann, Alex; Yang, Guang-Yu; Furuta, Glenn T.; Rothenberg, Marc E.; Pediatrics, School of MedicineEosinophilic gastrointestinal disorders (EGIDs) affect various segments of the gastrointestinal tract. Since these disorders are rare, collaboration is essential to enroll subjects in clinical studies and study the broader population. The Rare Diseases Clinical Research Network (RDCRN), a program of the National Center for Advancing Translational Sciences (NCATS), funded the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in 2014 to advance the field of EGIDs. CEGIR facilitates collaboration among various centers, subspecialties, patients, professional organizations and patient-advocacy groups and includes 14 clinical sites. It has successfully initiated two large multi-center clinical studies looking to refine EGID diagnoses and management. Several pilot studies are underway that focus on various aspects of EGIDs including novel therapeutic interventions, diagnostic and monitoring methods, and the role of the microbiome in pathogenesis. CEGIR currently nurtures five physician-scholars through a career training development program and has published more than 40 manuscripts since its inception. This review focuses on CEGIR's operating model and progress and how it facilitates a framework for exchange of ideas and stimulates research and innovation. This consortium provides a model for progress on other potential clinical areas.Item Development and Validation of Web-Based Tool to Predict Lamina Propria Fibrosis in Eosinophilic Esophagitis(Wolters Kluwer, 2022) Hiremath, Girish; Sun, Lili; Correa, Hernan; Acra, Sari; Collins, Margaret H.; Bonis, Peter; Arva, Nicoleta C.; Capocelli, Kelley E.; Falk, Gary W.; King, Eileen; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Mukkada, Vincent A.; Martin, Lisa J.; Putnam, Philip E.; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Aceves, Seema S.; Furuta, Glenn T.; Rothenberg, Marc E.; Koyama, Tatsuki; Dellon, Evan S.; Medicine, School of MedicineIntroduction: Approximately half of esophageal biopsies from patients with eosinophilic esophagitis (EoE) contain inadequate lamina propria, making it impossible to determine the lamina propria fibrosis (LPF). This study aimed to develop and validate a web-based tool to predict LPF in esophageal biopsies with inadequate lamina propria. Methods: Prospectively collected demographic and clinical data and scores for 7 relevant EoE histology scoring system epithelial features from patients with EoE participating in the Consortium of Eosinophilic Gastrointestinal Disease Researchers observational study were used to build the models. Using the least absolute shrinkage and selection operator method, variables strongly associated with LPF were identified. Logistic regression was used to develop models to predict grade and stage of LPF. The grade model was validated using an independent data set. Results: Of 284 patients in the discovery data set, median age (quartiles) was 16 (8-31) years, 68.7% were male patients, and 93.4% were White. Age of the patient, basal zone hyperplasia, dyskeratotic epithelial cells, and surface epithelial alteration were associated with presence of LPF. The area under the receiver operating characteristic curve for the grade model was 0.84 (95% confidence interval: 0.80-0.89) and for stage model was 0.79 (95% confidence interval: 0.74-0.84). Our grade model had 82% accuracy in predicting the presence of LPF in an external validation data set. Discussion: We developed parsimonious models (grade and stage) to predict presence of LPF in esophageal biopsies with inadequate lamina propria and validated our grade model. Our predictive models can be easily used in the clinical setting to include LPF in clinical decisions and determine its effect on treatment outcomes.Item Development of a Core Outcome Set for Therapeutic Studies in Eosinophilic Esophagitis (COREOS)(Elsevier, 2021) Ma, Christopher; Schoepfer, Alain M.; Dellon, Evan S.; Bredenoord, Albert J.; Chehade, Mirna; Collins, Margaret H.; Feagan, Brian G.; Furuta, Glenn T.; Gupta, Sandeep K.; Hirano, Ikuo; Jairath, Vipul; Katzka, David A.; Pai, Rish K.; Rothenberg, Marc E.; Straumann, Alex; Aceves, Seema S.; Alexander, Jeffrey A.; Arva, Nicoleta C.; Atkins, Dan; Biedermann, Luc; Blanchard, Carine; Cianferoni, Antonella; Ciriza de los Rios, Constanza; Clayton, Frederic; Davis, Carla M.; de Bortoli, Nicola; Dias, Jorge A.; Falk, Gary W.; Genta, Robert M.; Ghaffari, Gisoo; Gonsalves, Nirmala; Greuter, Thomas; Hopp, Russell; Hsu Blatman, Karen S.; Jensen, Elizabeth T.; Johnston, Doug; Kagalwalla, Amir F.; Larsson, Helen M.; Leung, John; Louis, Hubert; Masterson, Joanne C.; Menard-Katcher, Calies; Menard-Katcher, Paul A.; Moawad, Fouad J.; Muir, Amanda B.; Mukkada, Vincent A.; Penagini, Roberto; Pesek, Robert D.; Peterson, Kathryn; Putnam, Philip E.; Ravelli, Alberto; Savarino, Edoardo V.; Schlag, Christoph; Schreiner, Philipp; Simon, Dagmar; Smyrk, Thomas C.; Spergel, Jonathan M.; Taft, Tiffany H.; Terreehorst, Ingrid; Vanuytsel, Tim; Venter, Carina; Vieira, Mario C.; Vieth, Michael; Vlieg-Boerstra, Berber; von Arnim, Ulrike; Walker, Marjorie M.; Wechsler, Joshua B.; Woodland, Philip; Woosley, John T.; Yang, Guang-Yu; Zevit, Noam; Safroneeva, Ekaterina; Medicine, School of MedicineBackground End points used to determine treatment efficacy in eosinophilic esophagitis (EoE) have evolved over time. With multiple novel therapies in development for EoE, harmonization of outcomes measures will facilitate evidence synthesis and appraisal when comparing different treatments. Objective We sought to develop a core outcome set (COS) for controlled and observational studies of pharmacologic and diet interventions in adult and pediatric patients with EoE. Methods Candidate outcomes were generated from systematic literature reviews and patient engagement interviews and surveys. Consensus was established using an iterative Delphi process, with items voted on using a 9-point Likert scale and with feedback from other participants to allow score refinement. Consensus meetings were held to ratify the outcome domains of importance and the core outcome measures. Stakeholders were recruited internationally and included adult and pediatric gastroenterologists, allergists, dieticians, pathologists, psychologists, researchers, and methodologists. Results The COS consists of 4 outcome domains for controlled and observational studies: histopathology, endoscopy, patient-reported symptoms, and EoE-specific quality of life. A total of 69 stakeholders (response rate 95.8%) prioritized 42 outcomes in a 2-round Delphi process, and the final ratification meeting generated consensus on 33 outcome measures. These included measurement of the peak eosinophil count, Eosinophilic Esophagitis Histology Scoring System, Eosinophilic Esophagitis Endoscopic Reference Score, and patient-reported measures of dysphagia and quality of life. Conclusions This interdisciplinary collaboration involving global stakeholders has produced a COS that can be applied to adult and pediatric studies of pharmacologic and diet therapies for EoE and will facilitate meaningful treatment comparisons and improve the quality of data synthesis.Item Esophageal Epithelium and Lamina Propria Are Unevenly Involved in Eosinophilic Esophagitis(Elsevier, 2023-03-24) Hiremath, Girish; Sun, Lili; Collins, Margaret H.; Bonis, Peter A.; Arva, Nicoleta C.; Capocelli, Kelley E.; Chehade, Mirna; Davis, Carla M.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Leung, John; Khoury, Paneez; Mukkada, Vincent A.; Martin, Lisa J.; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Aceves, Seema S.; Furuta, Glenn T.; Rothenberg, Marc E.; Koyama, Tatsuki; Dellon, Evan S.; Medicine, School of MedicineBackground & Aims The 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. Methods Demographic, 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. Results EoEHSS 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). Conclusions Except 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.Item Evaluating Eosinophilic Colitis as a Unique Disease Using Colonic Molecular Profiles: A Multi-Site Study(Elsevier, 2022) Shoda, Tetsuo; Collins, Margaret H.; Rochman, Mark; Wen, Ting; Caldwell, Julie M.; Mack, Lydia E.; Osswald, Garrett A.; Besse, John A.; Haberman, Yael; Aceves, Seema S.; Arva, Nicoleta C.; Capocelli, Kelley E.; Chehade, Mirna; Davis, Carla M.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Khoury, Paneez; Klion, Amy; Menard-Katcher, Calies; Leung, John; Mukkada, Vincent; Putnam, Philip E.; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Furuta, Glenn T.; Denson, Lee A.; Rothenberg, Marc E.; Consortium of Eosinophilic Gastrointestinal Diseases Researchers (CEGIR); Pediatrics, School of MedicineBackground & aims: Colonic eosinophilia, an enigmatic finding often referred to as eosinophilic colitis (EoC), is a poorly understood condition. Whether EoC is a distinct disease or a colonic manifestation of eosinophilic gastrointestinal diseases (EGIDs) or inflammatory bowel disease (IBD) is undetermined. Methods: Subjects with EoC (n = 27) and controls (normal [NL, n = 20], Crohn's disease [CD, n = 14]) were enrolled across sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. EoC was diagnosed as colonic eosinophilia (ascending ≥100, descending ≥85, sigmoid ≥65 eosinophils/high-power field) with related symptoms. Colon biopsies were subjected to RNA sequencing. Associations between gene expression and histologic features were analyzed with Spearman correlation; operational pathways and cellular constituents were computationally derived. Results: We identified 987 differentially expressed genes (EoC transcriptome) between EoC and NL (>1.5-fold change, P < .05). Colonic eosinophil count correlated with 31% of EoC transcriptome, most notably with CCL11 and CLC (r = 0.78 and 0.77, P < .0001). Among EoC and other EGIDs, there was minimal transcriptomic overlap and minimal evidence of a strong allergic type 2 immune response in EoC compared with other EGIDs. Decreased cell cycle and increased apoptosis in EoC compared with NL were identified by functional enrichment analysis and immunostaining using Ki-67 and cleaved caspase-3. Pericryptal circumferential eosinophil collars were associated with the EoC transcriptome (P < .001). EoC transcriptome-based scores were reversible with disease remission and differentiated EoC from IBD, even after controlling for colonic eosinophil levels (P < .0001). Conclusions: We established EoC transcriptomic profiles, identified mechanistic pathways, and integrated findings with parallel IBD and EGID data. These findings establish EoC as a distinct disease compared with other EGIDs and IBD, thereby providing a basis for improving diagnosis and treatment.Item Genetic Alterations of NF-κB and Its Regulators: A Rich Platform to Advance Colorectal Cancer Diagnosis and Treatment(MDPI, 2023-12-21) Alipourgivi, Faranak; Motolani, Aishat; Qiu, Alice Y.; Qiang, Wenan; Yang, Guang-Yu; Chen, Shuibing; Lu, Tao; Pharmacology and Toxicology, School of MedicineColorectal cancer (CRC) is the third leading cause of cancer mortality in the United States, with an estimated 52,000 deaths in 2023. Though significant progress has been made in both diagnosis and treatment of CRC in recent years, genetic heterogeneity of CRC-the culprit for possible CRC relapse and drug resistance, is still an insurmountable challenge. Thus, developing more effective therapeutics to overcome this challenge in new CRC treatment strategies is imperative. Genetic and epigenetic changes are well recognized to be responsible for the stepwise development of CRC malignancy. In this review, we focus on detailed genetic alteration information about the nuclear factor (NF)-κB signaling, including both NF-κB family members, and their regulators, such as protein arginine methyltransferase 5 (PRMT5), and outer dynein arm docking complex subunit 2 (ODAD2, also named armadillo repeat-containing 4, ARMC4), etc., in CRC patients. Moreover, we provide deep insight into different CRC research models, with a particular focus on patient-derived xenografts (PDX) and organoid models, and their potential applications in CRC research. Genetic alterations on NF-κB signaling components are estimated to be more than 50% of the overall genetic changes identified in CRC patients collected by cBioportal for Cancer Genomics; thus, emphasizing its paramount importance in CRC progression. Consequently, various genetic alterations on NF-κB signaling may hold great promise for novel therapeutic development in CRC. Future endeavors may focus on utilizing CRC models (e.g., PDX or organoids, or isogenic human embryonic stem cell (hESC)-derived colonic cells, or human pluripotent stem cells (hPSC)-derived colonic organoids, etc.) to further uncover the underpinning mechanism of these genetic alterations in NF-κB signaling in CRC progression. Moreover, establishing platforms for drug discovery in dishes, and developing Biobanks, etc., may further pave the way for the development of innovative personalized medicine to treat CRC in the future.Item International consensus recommendations for eosinophilic gastrointestinal disease nomenclature(Elsevier, 2022-02-16) Dellon, Evan S.; Gonsalves, Nirmala; Abonia, J. Pablo; Alexander, Jeffrey A.; Arva, Nicoleta C.; Atkins, Dan; Attwood, Stephen E.; Auth, Marcus K.H.; Bailey, Dominique D.; Biederman, Luc; Blanchard, Carine; Bonis, Peter A.; Bose, Paroma; Bredenoord, Albert J.; Chang, Joy W.; Chehade, Mirna; Collins, Margaret H.; Di Lorenzo, Carlo; Dias, Jorge Amil; Dohil, Ranjan; Dupont, Christophe; Falk, Gary W.; Ferreira, Cristina T.; Fox, Adam T.; Genta, Robert M.; Greuter, Thomas; Gupta, Sandeep K.; Hirano, Ikuo; Hiremath, Girish S.; Horsley-Silva, Jennifer L.; Ishihara, Shunji; Ishimura, Norihisa; Jensen, Elizabeth T.; Gutiérrez-Junquera, Carolina; Katzka, David A.; Khoury, Paneez; Kinoshita, Yoshikazu; Kliewer, Kara L.; Koletzko, Sibylle; Leung, John; Liacouras, Chris A.; Lucendo, Alfredo J.; Martin, Lisa J.; McGowan, Emily C.; Menard-Katcher, Calies; Metz, David C.; Miller, Talya L.; Moawad, Fouad J.; Muir, Amanda B.; Mukkada, Vincent A.; Murch, Simon; Nhu, Quan M.; Nomura, Ichiro; Nurko, Samuel; Ohtsuka, Yoshikazu; Oliva, Salvatore; Orel, Rok; Papadopoulou, Alexandra; Patel, Dhyanesh A.; Pesek, Robert D.; Peterson, Kathryn A.; Philpott, Hamish; Putnam, Philip E.; Richter, Joel E.; Rosen, Rachel; Ruffner, Melanie A.; Safroneeva, Ekaterina; Schreiner, Philipp; Schoepfer, Alain; Schroeder, Shauna R.; Shah, Neil; Souza, Rhonda F.; Spechler, Stuart J.; Spergel, Jonathan M.; Straumann, Alex; Talley, Nicholas J.; Thapar, Nikhil; Vandenplas, Yvan; Venkatesh, Rajitha D.; Vieira, Mario C.; von Arnim, Ulrike; Walker, Marjorie M.; Wechsler, Joshua B.; Wershil, Barry K.; Wright, Benjamin L.; Yamada, Yoshiyuki; Yang, Guang-Yu; Zevit, Noam; Rothenberg, Marc E.; Furuta, Glenn T.; Aceves, Seema S.; Pediatrics, School of MedicineBackground & Aims Substantial heterogeneity in terminology used for eosinophilic gastrointestinal diseases (EGID), particularly the catchall term “eosinophilic gastroenteritis”, limits clinical and research advances. We aimed to achieve an international consensus for standardized EGID nomenclature. Methods This consensus process utilized Delphi methodology. An initial naming framework was proposed and refined in iterative fashion, then assessed in a first round of Delphi voting. Results were discussed in two consensus meetings, the framework was updated, and re-assessed in a second Delphi vote, with a 70% threshold set for agreement. Results Of 91 experts participating, 85 (93%) completed the first and 82 (90%) completed the second Delphi surveys. Consensus was reached on all but two statements. “EGID” was the preferred umbrella term for disorders of GI tract eosinophilic inflammation in the absence of secondary causes (100% agreement). Involved GI tract segments will be named specifically and use an “Eo” abbreviation convention: eosinophilic gastritis (now abbreviated EoG), eosinophilic enteritis (EoN), and eosinophilic colitis (EoC). The term “eosinophilic gastroenteritis” is no longer preferred as the overall name (96% agreement). When >2 GI tract areas are involved, the name should reflect all of the involved areas. Conclusions This international process resulted in consensus for updated EGID nomenclature for both clinical and research use. EGID will be the umbrella term rather than “eosinophilic gastroenteritis”, and specific naming conventions by location of GI tract involvement are recommended. As more data are developed, this framework can be updated to reflect best practices and the underlying science.Item Long-Lasting Dissociation of Esophageal Eosinophilia and Symptoms Following Dilation in Adults with Eosinophilic Esophagitis(Elsevier, 2021-05-29) Safroneeva, Ekaterina; Pan, Zhaoxing; King, Eileen; Martin, Lisa J.; Collins, Margaret H.; Yang, Guang-Yu; Capocelli, Kelley E.; Arva, Nicoleta C.; Abonia, J. Pablo; Atkins, Dan; Bonis, Peter A.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Leung, John; Menard-Katcher, Paul A.; Mukkada, Vincent A.; Schoepfer, Alain M.; Spergel, Jonathan M.; Wershil, Barry K.; Rothenberg, Marc E.; Aceves, Seema S.; Furuta, Glenn T.; Pediatrics, School of MedicineBackground and aims Esophageal dilation improves dysphagia but not inflammation in eosinophilic esophagitis (EoE) patients. We investigated if dilation modifies the association between symptoms and esophageal eosinophil count (eos/hpf). Methods Adults enrolled in a multisite, prospective Consortium of Gastrointestinal Eosinophilic Disease Researchers OMEGA observational study (NCT02523118) completed the symptom-based EoE activity index (EEsAI) patient-reported outcome instrument and underwent endoscopy with biopsies. Patients were stratified based on dilation status as absent, performed ≤1 and >1 year before endoscopy. Assessments included Spearman’s correlations of the relationship between symptoms and eos/hpf and linear regression with EEsAI as the outcome, eos/hpf as predictor, and interaction for dilation and eos/hpf. Results Amongst 100 patients (n=61 male, median age 37 years), 15 and 40 patients underwent dilation ≤1 year and >1 year before index endoscopy, respectively. In non-dilated patients, association between eos/hpf and symptoms was moderate (Rho=0.49, p-value<0.001); for 10 eos/hpf increase, the predicted EEsAI increased by 2.69 (p-value=0.002). In patients dilated ≤1 and >1 year before index endoscopy, this association was abolished (Rho=-0.38, p-value=0.157 for ≤1 year and Rho=0.02, p-value=0.883 >1 year); for 10 eos/hpf increase, the predicted EEsAI changed by -1.64 (p-value=0.183) and 0.78 (p-value=0.494), respectively). Dilation modifies association between symptoms and eos/hpf (p-value=0.005 and p-value=0.187 for interaction terms of eos/hpf and dilation ≤1 year and >1 year before index endoscopy, respectively). Conclusion In non-dilated EoE adults, eos/hpf correlates modestly with symptoms; this correlation was no longer appreciated in dilated patients, and the dilation effects lasted longer than one year. Dilation status should be considered in studies evaluating EoE treatment and for clinical follow-up.Item Loss of Endothelial TSPAN12 Promotes Fibrostenotic Eosinophilic Esophagitis via Endothelial Cell–Fibroblast Crosstalk(AGA, 2022-02) Shoda, Tetsuo; Wen, Ting; Caldwell, Julie M.; Morgenstern, Netali Ben-Baruch; Osswald, Garrett A.; Rochman, Mark; Mack, Lydia E.; Felton, Jennifer M.; Abonia, J. Pablo; Arva, Nicoleta C.; Atkina, Dan; Bonis, Peter A.; Capocelli, Kelley E.; Collins, Margaret H.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Leung, John; Menard-Katcher, Paul A.; Mukkada, Vincent A.; Putnam, Philip E.; Rudman Spergel, Amanda K.; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Aceves, Seema S.; Furuta, Glenn T.; Rothenberg, Marc E.; Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Investigators Group; Medicine, School of MedicineBackground & Aims Eosinophilic esophagitis (EoE) can progress to fibrostenosis by unclear mechanisms. Herein, we investigated gene dysregulation in fibrostenotic EoE, its association with clinical parameters and specific pathways, and the functional consequences. Methods Esophageal biopsies from subjects with EoE were collected across 11 Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) sites (n = 311) and two independent replication cohorts (n = 83). Inclusion criteria for fibrostenotic EoE were endoscopic rings, stricture, and/or a history of dilation. Endoscopic, histologic, and molecular features were assessed by the EoE endoscopic reference score (EREFS), EoE Histology Scoring System (HSS), EoE Diagnostic Panel (EDP), and RNA sequencing. Esophageal endothelial TSPAN12 expression and functional effects on barrier integrity and gene expression were analyzed in vitro. Results TSPAN12 was the gene most correlated with fibrostenosis (r = -0.40, P < .001). TSPAN12 was lower in fibrostenotic EoE and correlated with EREFS, EDP, and HSS (r = 0.34–0.47, P < .001). Lower TSPAN12 associated with smaller esophageal diameter (r = 0.44, P = .03), increased lamina propria fibrosis (r = -0.41, P < .001), and genes enriched in cell cycle–related pathways. IL-13 reduced TSPAN12 expression in endothelial cells. Conversely, anti-IL-13 therapy increased TSPAN12 expression. TSPAN12 gene silencing increased endothelial cell permeability and dysregulated genes associated with extracellular matrix (ECM) pathways. Endothelial cell–fibroblast crosstalk induced ECM changes relevant to esophageal remodeling. Conclusions Patients with fibrostenotic EoE express decreased levels of endothelial TSPAN12. We propose that IL-13 decreases TSPAN12, likely contributing to the chronicity of EoE by promoting tissue remodeling through fibroblast-endothelial cell crosstalk.Item Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis(Wiley, 2023) Furuta, Glenn T.; Fillon, Sophie A.; Williamson, Kayla M.; Robertson, Charles E.; Stevens, Mark J.; Aceves, Seema S.; Arva, Nicoleta C.; Chehade, Mirna; Collins, Margaret H.; Davis, Carla M.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Khoury, Paneez; Leung, John; Martin, Lisa J.; Menard-Katcher, Paul; Mukkada, Vincent A.; Peterson, Kathryn; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Rothenberg, Marc E.; Harris, J. Kirk; Pediatrics, School of MedicineObjective: The 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. Methods: We 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. Results: One 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. Conclusions: Dominant 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.