دورية أكاديمية
Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study.
| العنوان: | Eosinophilic oesophagitis endotype classification by molecular, clinical, and histopathological analyses: a cross-sectional study. |
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| المؤلفون: | Shoda T; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Wen T; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Aceves SS; Division of Allergy Immunology, University of California at San Diego, Rady Children's Hospital, San Diego, CA, USA., Abonia JP; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Atkins D; Division of Pediatric Allergy and Immunology, Children's Hospital Colorado, Denver, CO, USA., Bonis PA; Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA., Caldwell JM; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Capocelli KE; Department of Pathology, Children's Hospital Colorado, Aurora, CO, USA., Carpenter CL; Health Informatics Institute, Departments of Pediatrics and Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA., Collins MH; Division of Pathology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Dellon ES; Center for Esophageal Diseases and Swallowing, Division of Gastroenterology and Hepatology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA., Eby MD; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Gonsalves N; Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Gupta SK; Department of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois College of Medicine, Peoria, IL, USA., Falk GW; Division of Gastroenterology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA., Hirano I; Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Menard-Katcher P; Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Kuhl JT; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Krischer JP; Health Informatics Institute, Departments of Pediatrics and Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA., Leung J; Division of Gastroenterology, Tufts Medical Center, Boston, MA, USA., Mukkada VA; Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA., Spergel JM; Division of Allergy and Immunology, Children's Hospital of Philadelphia, Perelman School of Medicine at University of Pennsylvania, Philadelphia, PA, USA., Trimarchi MP; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Yang GY; Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Zimmermann N; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA., Furuta GT; Division Digestive Health Institute, Children's Hospital Colorado, Gastrointestinal Eosinophilic Diseases Program, University of Colorado School of Medicine, Aurora, CO, USA., Rothenberg ME; Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA. Electronic address: Rothenberg@cchmc.org. |
| مؤلفون مشاركون: | Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) |
| المصدر: | The lancet. Gastroenterology & hepatology [Lancet Gastroenterol Hepatol] 2018 Jul; Vol. 3 (7), pp. 477-488. Date of Electronic Publication: 2018 May 03. |
| نوع المنشور: | Journal Article; Multicenter Study; Observational Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier B.V Country of Publication: Netherlands NLM ID: 101690683 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2468-1253 (Electronic) NLM ISO Abbreviation: Lancet Gastroenterol Hepatol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Amsterdam] : Elsevier B.V., [2016]- |
| مواضيع طبية MeSH: | Eosinophilic Esophagitis/*classification , Eosinophilic Esophagitis/*pathology, Adolescent ; Adult ; Aged ; Biopsy ; Child ; Child, Preschool ; Cross-Sectional Studies ; Eosinophilic Esophagitis/genetics ; Esophagoscopy ; Female ; Gene Expression Profiling ; Humans ; Hyperplasia ; Leukocyte Count ; Machine Learning ; Male ; Middle Aged ; Phenotype ; Prospective Studies ; Severity of Illness Index ; Young Adult |
| مستخلص: | Background: Eosinophilic oesophagitis is understood in terms of quantifiable histological, endoscopic, and molecular features. Data are scant for inter-relations of these features and their potential to identify distinct disease endotypes. We aimed to identify clinical-pathological correlations between endoscopic and histological disease variables by transcription profiling of the oesophagus of patients with eosinophilic oesophagitis of varying severity and disease activity states. Methods: We did a cross-sectional study across ten hospital sites in the USA associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. We analysed oesophageal biopsy specimens taken from paediatric and adult patients with eosinophilic oesophagitis (discovery cohort), using the eosinophilic oesophagitis diagnostic panel (EDP), a set of 96 informative transcripts. Histological and endoscopic features were assessed by quantification of oesophageal eosinophils and use of the eosinophilic oesophagitis histology scoring system (HSS) and the eosinophilic oesophagitis endoscopic reference score (EREFS). Associations among the various histological, endoscopic, and molecular features were analysed by Spearman correlation. Results were replicated in a biologically independent, single-centre, validation cohort of patients with active eosinophilic oesophagitis. Findings: The discovery cohort contained 185 samples and the validation cohort comprised 100 specimens. In the discovery cohort, EDP showed intersite consistency, significant correlation with oesophageal eosinophils (p<0·0001), and similar findings between paediatric and adult patients. Of eight HSS domains, basal zone hyperplasia correlated with the EDP (median Spearman ρ 0·47 [IQR 0·36-0·60]). Of five EREFS features, distal furrows correlated with the EDP (median Spearman ρ 0·42 [0·32-0·50]). By analysing active eosinophilic oesophagitis in the discovery cohort, the EDP identified three clusters associated with distinct endotypes (termed EoEe1-3) despite similar eosinophil levels. EoEe1 was associated with a normal-appearing oesophagus (risk ratio [RR] 3·27, 95% CI 1·04-10·27; p=0·0443), an inverse association with a history of oesophageal dilation (0·27, 0·09-0·82; p=0·0105) and showed relatively mild histological, endoscopic, and molecular changes. EoEe2 showed an inflammatory and steroid-refractory phenotype (RR 2·77, 95% CI 1·11-6·95; p=0·0376) and had the highest expression of inflammatory cytokines and steroid-responding genes. EoEe3 was associated with a narrow-calibre oesophagus (RR 7·98, 95% CI 1·84-34·64; p=0·0013) and adult onset (2·22, 1·19-4·12; p=0·0155), and showed the highest degree of endoscopic and histological severity and the lowest expression of epithelial differentiation genes. These endotypes were replicated in the validation cohort by clustering and with an eosinophilic oesophagitis endotype-prediction algorithm. Interpretation: Our new disease classification stratifies patients with eosinophilic oesophagitis into subgroups with potential clinical and therapeutic significance and provides a framework for a precision medicine approach to eosinophilic oesophagitis. Funding: National Institutes of Health. (Copyright © 2018 Elsevier Ltd. All rights reserved.) |
| التعليقات: | Comment in: Lancet Gastroenterol Hepatol. 2018 Jul;3(7):449-450. (PMID: 29730082) |
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| معلومات مُعتمدة: | P30 DK078392 United States DK NIDDK NIH HHS; U01 TR001263 United States TR NCATS NIH HHS; U54 AI117804 United States AI NIAID NIH HHS |
| تواريخ الأحداث: | Date Created: 20180507 Date Completed: 20190206 Latest Revision: 20190701 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC5997568 |
| DOI: | 10.1016/S2468-1253(18)30096-7 |
| PMID: | 29730081 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2468-1253 |
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| DOI: | 10.1016/S2468-1253(18)30096-7 |