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Increased colonic expression of ACE2 associates with poor prognosis in Crohn's disease.
Toyonaga, Takahiko; Araba, Kenza C; Kennedy, Meaghan M; Keith, Benjamin P; Wolber, Elisabeth A; Beasley, Caroline; Steinbach, Erin C; Schaner, Matthew R; Jain, Animesh; Long, Millie D; Barnes, Edward L; Herfarth, Hans H; Isaacs, Kim L; Hansen, Jonathan J; Kapadia, Muneera R; Guillem, José Gaston; Gulati, Ajay S; Sethupathy, Praveen; Furey, Terrence S; Ehre, Camille; Sheikh, Shehzad Z.
  • Toyonaga T; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Araba KC; Department of Gastroenterology and Hepatology, The Jikei University School of Medicine, Tokyo, Japan.
  • Kennedy MM; Department of Genetics, Curriculum in Bioinformatics and Computational Biology, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.
  • Keith BP; Marsico Lung Institute, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.
  • Wolber EA; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Beasley C; Department of Genetics, Curriculum in Bioinformatics and Computational Biology, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.
  • Steinbach EC; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Schaner MR; Department of Genetics, Curriculum in Bioinformatics and Computational Biology, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.
  • Jain A; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Long MD; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Barnes EL; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Herfarth HH; Division of Rheumatology, Allergy and Immunology, Department of Medicine, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.
  • Isaacs KL; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Hansen JJ; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Kapadia MR; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Guillem JG; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Gulati AS; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Sethupathy P; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Furey TS; Center for Gastrointestinal Biology and Disease, University of North Carolina At Chapel Hill, 111 Mason Farm Road, 7312B MBRB, UNC Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Ehre C; Department of Surgery, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.
  • Sheikh SZ; Department of Surgery, University of North Carolina At Chapel Hill, Chapel Hill, NC, USA.
Sci Rep ; 11(1): 13533, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1387483
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Crohn Disease / Angiotensin-Converting Enzyme 2 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Adolescent / Adult / Female / Humans / Male / Young adult Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-92979-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Crohn Disease / Angiotensin-Converting Enzyme 2 Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study Limits: Adolescent / Adult / Female / Humans / Male / Young adult Language: English Journal: Sci Rep Year: 2021 Document Type: Article Affiliation country: S41598-021-92979-2