{"doi":"10.1101/2020.11.24.396382","title":"Increased Colonic Expression of ACE2 Associates with Poor Prognosis in Crohn’s disease","abstract":"Abstract Background and Aims 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. Methods We examined the expression of colon ACE2 using RNA-seq and quantitative (q) RT-PCR from 69 adult CD and 14 NIBD control patients. In a subset of this cohort 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. Results Colonic ACE2 expression was significantly higher in a subset of adult CD patients (ACE2-high CD). 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 diagnosis, with a Cox regression analysis finding that high ACE2 levels is an independent risk factor (OR 2.18; 95%CI, 1.05-4.55; p=0.037). Conclusion Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that may impact CD disease-related outcomes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121815,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9606,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":562550,"name":"Kenza C. Araba","orcid":null,"position":1,"is_corresponding":false},{"id":561985,"name":"Meaghan M. 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Barnes","orcid":"0000-0001-9894-8796","position":10,"is_corresponding":false},{"id":233525,"name":"Hans Herfarth","orcid":"0000-0003-4268-823X","position":11,"is_corresponding":false},{"id":218566,"name":"Kim L. Isaacs","orcid":"0000-0002-6433-876X","position":12,"is_corresponding":false},{"id":526094,"name":"Jonathan J. Hansen","orcid":null,"position":13,"is_corresponding":false},{"id":423691,"name":"Muneera R. Kapadia","orcid":"0000-0003-0382-880X","position":14,"is_corresponding":false},{"id":239555,"name":"José G. Guillem","orcid":"0009-0002-3510-8276","position":15,"is_corresponding":false},{"id":411872,"name":"Mark J. Koruda","orcid":"0000-0001-7098-6862","position":16,"is_corresponding":false},{"id":562553,"name":"Reza Rahbar","orcid":null,"position":17,"is_corresponding":false},{"id":562554,"name":"Tim Sadiq","orcid":null,"position":18,"is_corresponding":false},{"id":366377,"name":"Ajay Gulati","orcid":"0000-0002-7612-6369","position":19,"is_corresponding":false},{"id":460895,"name":"Praveen Sethupathy","orcid":"0000-0001-9887-8871","position":20,"is_corresponding":false},{"id":11678,"name":"Terrence S. Furey","orcid":"0000-0001-5546-9672","position":21,"is_corresponding":false},{"id":107105,"name":"Camille Ehré","orcid":"0000-0002-0046-0096","position":22,"is_corresponding":false},{"id":525087,"name":"Shehzad Z. 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