Altered Intestinal ACE2 Levels Are Associated With Inflammation, Severe Disease, and Response to Anti-Cytokine Therapy in Inflammatory Bowel Disease.
Altered Intestinal ACE2 Levels Are Associated With Inflammation, Severe Disease, and Response to Anti-Cytokine Therapy in Inflammatory Bowel Disease.
复制标题
DOI：
10.1053/j.gastro.2020.10.041
复制
发表时间：
2021-02
期刊：
影响因子：
29.4
通讯作者：
中科院分区：
文献类型：
--
作者：
严重急性呼吸综合征冠状病毒2型宿主受体血管紧张素转换酶2(ACE2)在小肠高表达。我们的目的是确定影响克罗恩病(CD)、溃疡性结肠炎(UC)和非炎症性肠病(IBD)对照组肠道ACE2表达的因素。采用批量RNA测序或微阵列技术分析ACE2与人口学特征、疾病活动性及预后的关系。我们在3个临床试验中检测了抗肿瘤坏死因子和抗IL-12/IL-23治疗对SB和结肠ACE2表达的影响。分别建立了单变量和多变量回归模型。与非IBD对照组相比，SB CD组ACE2水平持续降低，结肠性UC组ACE2水平持续升高。SB ACE2升高也与人口统计特征(年龄和体重指数升高)有关，与2019年冠状病毒病不良结局相关。在CD中，SB ACE2在随后发展为复杂疾病的患者中降低。在UC中，活动期疾病和随后需要抗肿瘤坏死因子抢救治疗的患者的结肠ACE2升高。活动期CD和UC的SB和结肠ACE2表达可通过抗细胞因子治疗恢复，尤其是在应答者。IBD中SB降低而结肠ACE2水平升高与炎症和严重疾病有关，但在抗细胞因子治疗后恢复正常，提示SB和结肠炎症中ACE2相关生物学分区。在严重急性呼吸综合征冠状病毒2型感染的背景下，通过抗细胞因子治疗恢复ACE2的表达可能是重要的，并可能解释使用抗细胞因子治疗的IBD患者2019年冠状病毒病发病率下降的报道。
The host receptor for severe acute respiratory syndrome coronavirus 2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small bowel (SB). Our aim was to identify factors influencing intestinal ACE2 expression in Crohn’s disease (CD), ulcerative colitis (UC), and non–inflammatory bowel disease (IBD) controls. Using bulk RNA sequencing or microarray transcriptomics from tissue samples (4 SB and 2 colonic cohorts; n = 495; n = 387 UC; n = 94 non-IBD), we analyzed the relationship between ACE2 with demographics and disease activity and prognosis. We examined the outcome of anti–tumor necrosis factor and anti–interleukin-12/interleukin-23 treatment on SB and colonic ACE2 expression in 3 clinical trials. Univariate and multivariate regression models were fitted. ACE2 levels were consistently reduced in SB CD and elevated in colonic UC compared with non-IBD controls. Elevated SB ACE2 was also associated with demographic features (age and elevated body mass index) associated with poor coronavirus disease 2019 outcomes. Within CD, SB ACE2 was reduced in patients subsequently developing complicated disease. Within UC, colonic ACE2 was elevated in active disease and in patients subsequently requiring anti–tumor necrosis factor rescue therapy. SB and colonic ACE2 expression in active CD and UC were restored by anti-cytokine therapy, most notably in responders. Reduced SB but elevated colonic ACE2 levels in IBD are associated with inflammation and severe disease, but normalized after anti-cytokine therapy, suggesting compartmentalization of ACE2-related biology in SB and colonic inflammation. The restoration of ACE2 expression with anti-cytokine therapy might be important in the context of severe acute respiratory syndrome coronavirus 2 infection and potentially explain reports of reduced morbidity from coronavirus disease 2019 in IBD patients treated with anti-cytokines.
登录
查看更多内容
ACE2将氨基酸营养不良与微生物生态学和肠炎联系起来。
影响因子：
64.8
作者：
Hashimoto T;Perlot T;Rehman A;Trichereau J;Ishiguro H;Paolino M;Sigl V;Hanada T;Hanada R;Lipinski S;Wild B;Camargo SM;Singer D;Richter A;Kuba K;Fukamizu A;Schreiber S;Clevers H;Verrey F;Rosenstiel P;Penninger JM
通讯作者：
Penninger JM
影响因子：
16.6
作者：
Haberman, Yael;Karns, Rebekah;Denson, Lee A.
通讯作者：
Denson, Lee A.
影响因子：
29.4
作者：
Nikolaus, Susanna;Schulte, Berenice;Schreiber, Stefan
通讯作者：
Schreiber, Stefan
影响因子：
29
作者：
Nagareddy PR;Kraakman M;Masters SL;Stirzaker RA;Gorman DJ;Grant RW;Dragoljevic D;Hong ES;Abdel-Latif A;Smyth SS;Choi SH;Korner J;Bornfeldt KE;Fisher EA;Dixit VD;Tall AR;Goldberg IJ;Murphy AJ
通讯作者：
Murphy AJ
DOI：
10.1016/s0140-6736(17)30317-3
发表时间：
2017-04-29
期刊：
Lancet (London, England)
影响因子：
--
作者：
Kugathasan S;Denson LA;Walters TD;Kim MO;Marigorta UM;Schirmer M;Mondal K;Liu C;Griffiths A;Noe JD;Crandall WV;Snapper S;Rabizadeh S;Rosh JR;Shapiro JM;Guthery S;Mack DR;Kellermayer R;Kappelman MD;Steiner S;Moulton DE;Keljo D;Cohen S;Oliva-Hemker M;Heyman MB;Otley AR;Baker SS;Evans JS;Kirschner BS;Patel AS;Ziring D;Trapnell BC;Sylvester FA;Stephens MC;Baldassano RN;Markowitz JF;Cho J;Xavier RJ;Huttenhower C;Aronow BJ;Gibson G;Hyams JS;Dubinsky MC
通讯作者：
Dubinsky MC