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 leve...
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Nature Portfolio
2021
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oai:doaj.org-article:46dc769554ff4a93a33f60385762e0c72021-12-02T16:32:12ZIncreased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease10.1038/s41598-021-92979-22045-2322https://doaj.org/article/46dc769554ff4a93a33f60385762e0c72021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92979-2https://doaj.org/toc/2045-2322Abstract 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.Takahiko ToyonagaKenza C. ArabaMeaghan M. KennedyBenjamin P. KeithElisabeth A. WolberCaroline BeasleyErin C. SteinbachMatthew R. SchanerAnimesh JainMillie D. LongEdward L. BarnesHans H. HerfarthKim L. IsaacsJonathan J. HansenMuneera R. KapadiaJosé Gaston GuillemAjay S. GulatiPraveen SethupathyTerrence S. FureyCamille EhreShehzad Z. SheikhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021) |
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DOAJ |
| collection |
DOAJ |
| language |
EN |
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Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Takahiko Toyonaga Kenza C. Araba Meaghan M. Kennedy Benjamin P. Keith Elisabeth A. Wolber Caroline Beasley Erin C. Steinbach Matthew R. Schaner Animesh Jain Millie D. Long Edward L. Barnes Hans H. Herfarth Kim L. Isaacs Jonathan J. Hansen Muneera R. Kapadia José Gaston Guillem Ajay S. Gulati Praveen Sethupathy Terrence S. Furey Camille Ehre Shehzad Z. Sheikh Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease |
| description |
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. |
| format |
article |
| author |
Takahiko Toyonaga Kenza C. Araba Meaghan M. Kennedy Benjamin P. Keith Elisabeth A. Wolber Caroline Beasley Erin C. Steinbach Matthew R. Schaner Animesh Jain Millie D. Long Edward L. Barnes Hans H. Herfarth Kim L. Isaacs Jonathan J. Hansen Muneera R. Kapadia José Gaston Guillem Ajay S. Gulati Praveen Sethupathy Terrence S. Furey Camille Ehre Shehzad Z. Sheikh |
| author_facet |
Takahiko Toyonaga Kenza C. Araba Meaghan M. Kennedy Benjamin P. Keith Elisabeth A. Wolber Caroline Beasley Erin C. Steinbach Matthew R. Schaner Animesh Jain Millie D. Long Edward L. Barnes Hans H. Herfarth Kim L. Isaacs Jonathan J. Hansen Muneera R. Kapadia José Gaston Guillem Ajay S. Gulati Praveen Sethupathy Terrence S. Furey Camille Ehre Shehzad Z. Sheikh |
| author_sort |
Takahiko Toyonaga |
| title |
Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease |
| title_short |
Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease |
| title_full |
Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease |
| title_fullStr |
Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease |
| title_full_unstemmed |
Increased colonic expression of ACE2 associates with poor prognosis in Crohn’s disease |
| title_sort |
increased colonic expression of ace2 associates with poor prognosis in crohn’s disease |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/46dc769554ff4a93a33f60385762e0c7 |
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