@article{3aa7b552e031422ab9231b6474cd2401,
title = "Targeted Assessment of Mucosal Immune Gene Expression Predicts Clinical Outcomes in Children with Ulcerative Colitis",
abstract = "Background and Aims: We aimed to determine whether a targeted gene expression panel could predict clinical outcomes in paediatric ulcerative colitis [UC] and investigated putative pathogenic roles of predictive genes. Methods: In total, 313 rectal RNA samples from a cohort of newly diagnosed paediatric UC patients (PROTECT) were analysed by a real-time PCR microfluidic array for expression of type 1, 2 and 17 inflammation genes. Associations between expression and clinical outcomes were assessed by logistic regression. Identified prognostic markers were further analysed using existing RNA sequencing (RNA-seq) data sets and tissue immunostaining. Results: IL13RA2 was associated with a lower likelihood of corticosteroid-free remission (CSFR) on mesalamine at week 52 (p=.002). A model including IL13RA2 and only baseline clinical parameters was as accurate as an established clinical model, which requires week 4 remission status. RORC was associated with a lower likelihood of colectomy by week 52. A model including RORC and PUCAI predicted colectomy by 52 weeks (area under the receiver operating characteristic curve 0.71). Bulk RNA-seq identified IL13RA2 and RORC as hub genes within UC outcome-associated expression networks related to extracellular matrix and innate immune response, and lipid metabolism and microvillus assembly, respectively. Adult UC single-cell RNA-seq data revealed IL13RA2 and RORC co-expressed genes were localized to inflammatory fibroblasts and undifferentiated epithelial cells, respectively, which was supported by protein immunostaining. Conclusion: Targeted assessment of rectal mucosal immune gene expression predicts 52-week CSFR in treatment-na{\"i}ve paediatric UC patients. Further exploration of IL-13R2 as a therapeutic target in UC and future studies of the epithelial-specific role of RORC in UC pathogenesis are warranted.",
keywords = "Paediatric inflammatory bowel disease, gene expression array, weighted gene co-expression network analysis",
author = "Kathryn Clarkston and Rebekah Karns and Jegga, {Anil G.} and Mihika Sharma and Sejal Fox and Ojo, {Babajide A.} and Phillip Minar and Walters, {Thomas D.} and Griffiths, {Anne M.} and Mack, {David R.} and Brendan Boyle and Leleiko, {Neal S.} and James Markowitz and Rosh, {Joel R.} and Patel, {Ashish S.} and Sapana Shah and Baldassano, {Robert N.} and Marian Pfefferkorn and Cary Sauer and Subra Kugathasan and Yael Haberman and Hyams, {Jeffrey S.} and Denson, {Lee A.} and Rosen, {Michael J.}",
note = "Publisher Copyright: {\textcopyright} 2022 The Author(s). Published by Oxford University Press on behalf of European Crohn's and Colitis Organisation. All rights reserved.",
year = "2022",
month = nov,
day = "1",
doi = "10.1093/ecco-jcc/jjac075",
language = "אנגלית",
volume = "16",
pages = "1735--1750",
journal = "Journal of Crohn's and Colitis",
issn = "1873-9946",
publisher = "Oxford University Press",
number = "11",
}