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Increased colonic expression of ACE2 associates with poor prognosis in Crohn's 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.

SUBMITTER: Toyonaga T

PROVIDER: S-EPMC8241995 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Toyonaga Takahiko T Araba Kenza C KC Kennedy Meaghan M MM Keith Benjamin P BP Wolber Elisabeth A EA Beasley Caroline C Steinbach Erin C EC Schaner Matthew R MR Jain Animesh A Long Millie D MD Barnes Edward L EL Herfarth Hans H HH Isaacs Kim L KL Hansen Jonathan J JJ Kapadia Muneera R MR Guillem José Gaston JG Gulati Ajay S AS Sethupathy Praveen P Furey Terrence S TS Ehre Camille C Sheikh Shehzad Z SZ

Scientific reports 20210629 1

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 ...[more]

PMID: 34188154

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

Publications

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

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