Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn's disease

Alka A Potdar; Shishir Dube; Takeo Naito; Gregory Botwin; Talin Haritunians; Dalin Li; Shaohong Yang; Janine Bilsborough; Lee A Denson; Mark Daly; Stephan R Targan; Phillip Fleshner; Jonathan Braun; Subra Kugathasan; Thaddeus S Stappenbeck; Dermot P B McGovern

doi:10.1101/2020.04.19.20070995

Reduced expression of COVID-19 host receptor, ACE2 is associated with small bowel inflammation, more severe disease, and response to anti-TNF therapy in Crohn's disease

medRxiv [Preprint]. 2020 Apr 23:2020.04.19.20070995. doi: 10.1101/2020.04.19.20070995.

Authors

Alka A Potdar¹, Shishir Dube¹, Takeo Naito¹, Gregory Botwin¹, Talin Haritunians¹, Dalin Li¹, Shaohong Yang¹, Janine Bilsborough¹, Lee A Denson², Mark Daly³, Stephan R Targan¹, Phillip Fleshner¹, Jonathan Braun¹, Subra Kugathasan⁴, Thaddeus S Stappenbeck⁵, Dermot P B McGovern¹

Affiliations

¹ F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
² Division of Pediatric Gastroenterology, Hepatology, and nutrition, Department of Pediatrics, University of Cincinnati college of Medicine and the Cincinnati children's Hospital Medical center, Cincinnati, OH, USA.
³ Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
⁴ Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA; Children's Healthcare of Atlanta, Atlanta, GA, USA.
⁵ Department of Inflammation and Immunity, Cleveland Clinic, Cleveland, Ohio, USA.

Abstract

Angiotensin-Converting Enzyme 2 ( ACE2 ) has been identified as the host receptor for SARS-coronavirus 2 (SARS-CoV-2) which has infected millions world-wide and likely caused hundreds of thousands of deaths. Utilizing transcriptomic data from four cohorts taken from Crohn's disease (CD) and non-inflammatory bowel disease (IBD) subjects, we observed evidence of increased ACE2 mRNA in ileum with demographic features that have been associated with poor outcomes in COVID-19 including age and raised BMI. ACE2 was downregulated in CD compared to controls in independent cohorts. Within CD, ACE2 expression was reduced in inflamed ileal tissue and also remarkably, from uninvolved tissue in patients with a worse prognosis in both adult and pediatric cohorts. In active CD, small bowel ACE2 expression was restored by anti-TNF therapy particularly in anti-TNF responders. Collectively our data suggest that ACE2 downregulation is associated with inflammation and worse outcomes in CD.

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Abstract

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