作者
Tetsuo Shoda,Ting Wen,Julie M. Caldwell,Netali Ben-Baruch Morgenstern,Garrett A. Osswald,Mark Rochman,Lydia E Mack,Jennifer M Felton,J. Pablo Abonia,Nicoleta C. Arva,Dan Atkins,Peter A Bonis,Kelley E. Capocelli,Margaret H. Collins,Evan S. Dellon,Gary W. Falk,Nirmala Gonsalves,Sandeep K. Gupta,Ikuo Hirano,John Leung,Paul Menard-Katcher,Vincent A. Mukkada,Philip E. Putnam,Amanda K. Rudman Spergel,Jonathan M. Spergel,Joshua B. Wechsler,Guang Yu Yang,Seema S. Aceves,Glenn T. Furuta,Marc E. Rothenberg
摘要
ABSTRACT Background & 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 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.