Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease

Public Deposited
Analytics

Downloadable Content

Download PDF
Request Version for Screen Reader
Creator
  • Toyonaga, Takahiko
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Araba, Kenza C.
    • Affiliation: School of Medicine, Department of Genetics
  • Kennedy, Meaghan M.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Keith, Benjamin P.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Wolber, Elisabeth A.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Beasley, Caroline
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Steinbach, Erin C.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Schaner, Matthew R.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Jain, Animesh
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Long, Millie D.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Barnes, Edward L.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Herfarth, Hans H.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Isaacs, Kim L.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Hansen, Jonathan J.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Kapadia, Muneera R.
    • Affiliation: School of Medicine, Department of Surgery
  • Guillem, José Gaston
    • Affiliation: School of Medicine, Department of Surgery
  • Gulati, Ajay S.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Sethupathy, Praveen
    • Other Affiliation: Cornell University
  • Furey, Terrence S.
    • Affiliation: Center for Gastrointestinal Biology and Disease
  • Ehre, Camille
    • Affiliation: School of Medicine, Marsico Lung Institute/UNC Cystic Fibrosis Center
  • Sheikh, Shehzad Z.
    • Affiliation: Center for Gastrointestinal Biology and Disease
Abstract
  • The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan–Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10–4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.
Date of publication
Keyword
DOI
Identifier
Resource type
  • Article
Rights statement
  • In Copyright
License
  • Attribution 3.0 United States
Journal title
  • Scientific Reports
Journal volume
  • 11
Journal issue
  • 1
Language
  • English
Version
  • Publisher
ISSN
  • 2045-2322

Relations

Parents:

This work has no parents.

In Collection:

Items

Thumbnail Title Date Uploaded Visibility Actions
file details s41598-021-92979-2.pdf 2021-07-07 Public Download