• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

在慢性难治性袋炎患者中，维多珠单抗可阻断T细胞通过α4β7整合素依赖性方式与黏膜地址素细胞黏附分子-1（MAdCAM-1）的黏附。

α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis.

作者信息

Melde Michaela, Müller Tanja M, Schneider Ines, Geppert Carol-Immanuel, Mühl Laura, Besendorf Laura, Allner Clarissa, Becker Emily, Atreya Imke, Vitali Francesco, Atreya Raja, Neurath Markus F, Zundler Sebastian

机构信息

Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.

出版信息

Therap Adv Gastroenterol. 2021 Nov 24;14:17562848211054707. doi: 10.1177/17562848211054707. eCollection 2021.

DOI:10.1177/17562848211054707
PMID:34868349
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8640978/
Abstract

BACKGROUND

The anti-α4β7 integrin antibody vedolizumab is an established therapeutic option for the treatment of inflammatory bowel disease (IBD). It has also been successfully used in patients with chronic antibiotic-refractory pouchitis following proctocolectomey with ileal pouch-anal anastomosis. However, the expression and function of gut-homing markers as well as strategies to predict the response to vedolizumab in pouchitis are understudied so far.

METHODS

We used flow cytometry and dynamic adhesion assays to study the expression and function of gut-homing integrins on T cells from patients with pouchitis and controls as well as longitudinally during therapy of pouchitis with vedolizumab. Moreover, we describe clinical effects of vedolizumab in a cohort of patients with pouchitis.

RESULTS

T cells from patients with pouchitis express a specific profile of gut-homing integrins. Integrin α4β7 on T cells from patients with pouchitis mediates adhesion to mucosal addressin cell adhesion molecule (MAdCAM)-1, which can be blocked by vedolizumab . Vedolizumab efficiently treats pouchitis in a portion of patients and response correlates with dynamic adhesion profiles to MAdCAM-1.

CONCLUSION

Our data suggest that T cell trafficking seems to be important for the pathogenesis of pouchitis and support the therapeutic use of vedolizumab. Integrin function might serve as a biomarker to predict response to vedolizumab.

摘要

背景

抗α4β7整合素抗体维多珠单抗是治疗炎症性肠病（IBD）的既定治疗选择。它也已成功用于接受回肠储袋肛管吻合术的直肠结肠切除术后患有慢性抗生素难治性储袋炎的患者。然而，迄今为止，肠道归巢标志物的表达和功能以及预测储袋炎患者对维多珠单抗反应的策略尚未得到充分研究。

方法

我们使用流式细胞术和动态黏附试验来研究储袋炎患者和对照者T细胞上肠道归巢整合素的表达和功能，以及在维多珠单抗治疗储袋炎期间的纵向变化。此外，我们描述了维多珠单抗在一组储袋炎患者中的临床疗效。

结果

储袋炎患者的T细胞表达特定的肠道归巢整合素谱。储袋炎患者T细胞上的整合素α4β7介导对黏膜地址素细胞黏附分子（MAdCAM）-1的黏附，这可被维多珠单抗阻断。维多珠单抗可有效治疗部分患者的储袋炎，且反应与对MAdCAM-1的动态黏附谱相关。

结论

我们的数据表明，T细胞迁移似乎对储袋炎的发病机制很重要，并支持维多珠单抗的治疗应用。整合素功能可能作为预测对维多珠单抗反应的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/1f078da167af/10.1177_17562848211054707-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/2dcdf0e2a044/10.1177_17562848211054707-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/d3628b26efb3/10.1177_17562848211054707-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/d9c73a5f514f/10.1177_17562848211054707-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/1f078da167af/10.1177_17562848211054707-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/2dcdf0e2a044/10.1177_17562848211054707-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/d3628b26efb3/10.1177_17562848211054707-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/d9c73a5f514f/10.1177_17562848211054707-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe7e/8640978/1f078da167af/10.1177_17562848211054707-fig4.jpg

相似文献

1
α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis.在慢性难治性袋炎患者中，维多珠单抗可阻断T细胞通过α4β7整合素依赖性方式与黏膜地址素细胞黏附分子-1（MAdCAM-1）的黏附。
Therap Adv Gastroenterol. 2021 Nov 24;14:17562848211054707. doi: 10.1177/17562848211054707. eCollection 2021.
2
Vedolizumab blocks α4β7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis.维多珠单抗可阻断微小性结肠炎中α4β7整合素介导的T细胞与黏膜地址素细胞黏附分子-1的黏附。
Therap Adv Gastroenterol. 2022 Jun 28;15:17562848221098899. doi: 10.1177/17562848221098899. eCollection 2022.
3
Expression of MAdCAM-1 and Gut-homing T Cells in Inflamed Pouch Mucosa.黏附分子-1 和肠道归巢 T 细胞在炎症性袋状黏膜中的表达。
J Crohns Colitis. 2021 Sep 25;15(9):1491-1499. doi: 10.1093/ecco-jcc/jjab041.
4
Vedolizumab Antagonizes MAdCAM-1-Dependent Human Placental Cytotrophoblast Adhesion and Invasion In Vitro.维得利珠单抗拮抗 MAdCAM-1 依赖性人胎盘细胞滋养层黏附和侵袭的体外研究。
Inflamm Bowel Dis. 2022 Aug 1;28(8):1219-1228. doi: 10.1093/ibd/izac056.
5
Baseline levels of dynamic CD4 T cell adhesion to MAdCAM-1 correlate with clinical response to vedolizumab treatment in ulcerative colitis: a cohort study.基线水平的动态 CD4 T 细胞与 MAdCAM-1 的黏附与 vedolizumab 治疗溃疡性结肠炎的临床应答相关：一项队列研究。
BMC Gastroenterol. 2020 Apr 15;20(1):103. doi: 10.1186/s12876-020-01253-8.
6
Non-classical monocyte homing to the gut via α4β7 integrin mediates macrophage-dependent intestinal wound healing.非经典单核细胞通过 α4β7 整合素归巢至肠道，介导巨噬细胞依赖性肠道伤口愈合。
Gut. 2020 Feb;69(2):252-263. doi: 10.1136/gutjnl-2018-316772. Epub 2019 May 15.
7
MAdCAM-1 Costimulates T Cells through Integrin αβ to Cause Gene Expression Events Resembling Costimulation through CD28.黏膜地址素细胞黏附分子-1（MAdCAM-1）通过整合素αβ共刺激T细胞，引发类似于通过CD28共刺激的基因表达事件。
Immunohorizons. 2022 Mar 10;6(3):211-223. doi: 10.4049/immunohorizons.2200009.
8
Blocking GPR15 Counteracts Integrin-dependent T Cell Gut Homing in Vivo.阻断 GPR15 可拮抗整合素依赖性 T 细胞体内归巢。
J Crohns Colitis. 2024 Aug 6;18(7):1162-1172. doi: 10.1093/ecco-jcc/jjae012.
9
Vedolizumab for chronic antibiotic-refractory pouchitis.维多珠单抗用于治疗慢性抗生素难治性袋状结肠炎。
Gastroenterol Rep (Oxf). 2019 Apr;7(2):121-126. doi: 10.1093/gastro/goz001. Epub 2019 Jan 31.
10
Association of Vedolizumab Level, Anti-Drug Antibodies, and α4β7 Occupancy With Response in Patients With Inflammatory Bowel Diseases. vedolizumab 水平、抗药物抗体和 α4β7 占有率与炎症性肠病患者反应的相关性。
Clin Gastroenterol Hepatol. 2018 May;16(5):697-705.e7. doi: 10.1016/j.cgh.2017.11.050. Epub 2017 Dec 7.

引用本文的文献

1
The Force-Dependent Mechanism of an Integrin α4β7-MAdCAM-1 Interaction.整合素 α4β7 与 MAdCAM-1 相互作用的力依赖性机制。
Int J Mol Sci. 2023 Nov 7;24(22):16062. doi: 10.3390/ijms242216062.

本文引用的文献

1
An expert consensus to standardise clinical, endoscopic and histologic items and inclusion and outcome criteria for evaluation of pouchitis disease activity in clinical trials.评估临床研究中袋炎疾病活动的临床、内镜和组织学项目以及纳入和结局标准的专家共识。
Aliment Pharmacol Ther. 2021 May;53(10):1108-1117. doi: 10.1111/apt.16328. Epub 2021 Mar 18.
2
Expression of MAdCAM-1 and Gut-homing T Cells in Inflamed Pouch Mucosa.黏附分子-1 和肠道归巢 T 细胞在炎症性袋状黏膜中的表达。
J Crohns Colitis. 2021 Sep 25;15(9):1491-1499. doi: 10.1093/ecco-jcc/jjab041.
3
Baseline levels of dynamic CD4 T cell adhesion to MAdCAM-1 correlate with clinical response to vedolizumab treatment in ulcerative colitis: a cohort study.
基线水平的动态 CD4 T 细胞与 MAdCAM-1 的黏附与 vedolizumab 治疗溃疡性结肠炎的临床应答相关：一项队列研究。
BMC Gastroenterol. 2020 Apr 15;20(1):103. doi: 10.1186/s12876-020-01253-8.
4
Outcome of biological therapies in chronic antibiotic-refractory pouchitis: A retrospective single-centre experience.慢性抗生素难治性 pouchitis 中生物治疗的结果：回顾性单中心经验。
United European Gastroenterol J. 2019 Nov;7(9):1215-1225. doi: 10.1177/2050640619871797. Epub 2019 Aug 20.
5
Effectiveness of vedolizumab treatment in two different anti-tumor necrosis factor alpha refractory pouchitis: A case report.维多珠单抗治疗两种不同的抗肿瘤坏死因子α难治性袋状结肠炎的有效性：一例报告。
World J Clin Cases. 2019 Aug 26;7(16):2316-2321. doi: 10.12998/wjcc.v7.i16.2316.
6
Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances.免疫细胞在炎症性肠病中的迁移和滞留：机制见解和治疗进展。
Gut. 2019 Sep;68(9):1688-1700. doi: 10.1136/gutjnl-2018-317977. Epub 2019 May 24.
7
Vedolizumab for chronic antibiotic-refractory pouchitis.维多珠单抗用于治疗慢性抗生素难治性袋状结肠炎。
Gastroenterol Rep (Oxf). 2019 Apr;7(2):121-126. doi: 10.1093/gastro/goz001. Epub 2019 Jan 31.
8
Efficacy of Vedolizumab for Refractory Pouchitis of the Ileo-anal Pouch: Results From a Multicenter US Cohort.维多利珠单抗治疗回肠贮袋炎的疗效：来自美国多中心队列研究的结果。
Inflamm Bowel Dis. 2019 Aug 20;25(9):1569-1576. doi: 10.1093/ibd/izz030.
9
Adalimumab in the treatment of chronic pouchitis. A randomized double-blind, placebo-controlled trial.阿达木单抗治疗慢性袋炎。一项随机双盲、安慰剂对照试验。
Scand J Gastroenterol. 2019 Feb;54(2):188-193. doi: 10.1080/00365521.2019.1569718. Epub 2019 Feb 10.
10
Similar Inhibition of Dynamic Adhesion of Lymphocytes From IBD Patients to MAdCAM-1 by Vedolizumab and Etrolizumab-s.维得利珠单抗和埃妥珠单抗对炎症性肠病患者淋巴细胞与黏膜地址素细胞黏附分子-1动态黏附的抑制作用相似。
Inflamm Bowel Dis. 2018 May 18;24(6):1237-1250. doi: 10.1093/ibd/izy077.