Increased colonic expression of ACE2 associates with poor prognosis in Crohn's disease.
Increased colonic expression of ACE2 associates with poor prognosis in Crohn's disease.
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DOI：
10.1038/s41598-021-92979-2
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发表时间：
2021-06-29
影响因子：
4.6
通讯作者：
Sheikh SZ
中科院分区：
文献类型：
--
作者：
Toyonaga T;Araba KC;Kennedy MM;Keith BP;Wolber EA;Beasley C;Steinbach EC;Schaner MR;Jain A;Long MD;Barnes EL;Herfarth HH;Isaacs KL;Hansen JJ;Kapadia MR;Guillem JG;Gulati AS;Sethupathy P;Furey TS;Ehre C;Sheikh SZ
SARS-CoV-2的宿主受体血管紧张素转换酶2 （ACE2）在小肠中高度表达。我们的目的是研究在克罗恩病（CD）和非炎症性肠病（非ibd）对照中结肠ACE2的表达。我们假设ACE2的结肠表达水平影响CD病程。我们使用RNA-seq和定量RT-PCR检测了67例成年CD患者和14例NIBD对照患者结肠ACE2的表达。我们利用免疫组织化学方法验证了ACE2蛋白在福尔马林固定、石蜡包埋的匹配结肠和回肠组织中的表达和定位。通过多元回归分析和Kaplan-Meier估计来评估CD中ACE2表达增加对手术风险的影响。为了为我们研究结果的普遍性提供关键支持，我们分析了先前发表的来自两个大型独立CD患者队列的RNA-seq数据。在成年CD患者的一个亚群中，结肠ACE2表达显著升高，该亚群被定义为ACE2高CD亚群。在ACE2高CD患者样本中的免疫组化证实，与ACE2低CD和NIBD患者相比，结肠和回肠中ACE2蛋白表达较高。值得注意的是，我们发现ACE2高的CD患者在CD诊断后5年内接受手术的可能性显著增加，Cox回归分析发现，高ACE2水平是手术的独立危险因素（OR 2.17; 95% CI, 1.10-4.26; p = 0.025）。肠道ACE2表达增加与CD患者临床预后恶化相关。这些数据表明需要分子分层来影响乳糜泻相关的结果。
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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DOI：
10.1093/ecco-jcc/jjaa185
发表时间：
2021-03-05
期刊：
Journal of Crohn's & colitis
影响因子：
--
作者：
Verstockt B;Verstockt S;Abdu Rahiman S;Ke BJ;Arnauts K;Cleynen I;Sabino J;Ferrante M;Matteoli G;Vermeire S
通讯作者：
Vermeire S
影响因子：
5.9
作者：
Levy, David E.;Marie, Isabelle J.;Durbin, Joan E.
通讯作者：
Durbin, Joan E.
影响因子：
29.4
作者：
通讯作者：
--
影响因子：
8
作者：
Keith, Benjamin P.;Barrow, Jasmine B.;Sheikh, Shehzad Z.
通讯作者：
Sheikh, Shehzad Z.
影响因子：
4.9
作者：
Tinsley, Andrew;Navabi, Seyedehsan;Clarke, Kofi
通讯作者：
Clarke, Kofi