α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis
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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
SAGE Publishing
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/66d7a961a1bc4e629574dec05f820ce5 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:66d7a961a1bc4e629574dec05f820ce5 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:66d7a961a1bc4e629574dec05f820ce52021-12-01T23:33:19Zα4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis1756-284810.1177/17562848211054707https://doaj.org/article/66d7a961a1bc4e629574dec05f820ce52021-11-01T00:00:00Zhttps://doi.org/10.1177/17562848211054707https://doaj.org/toc/1756-2848Background: 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 in vitro . 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.Michaela MeldeTanja M. MüllerInes SchneiderCarol-Immanuel GeppertLaura MühlLaura BesendorfClarissa AllnerEmily BeckerImke AtreyaFrancesco VitaliRaja AtreyaMarkus F. NeurathSebastian ZundlerSAGE PublishingarticleDiseases of the digestive system. GastroenterologyRC799-869ENTherapeutic Advances in Gastroenterology, Vol 14 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Diseases of the digestive system. Gastroenterology RC799-869 |
| spellingShingle |
Diseases of the digestive system. Gastroenterology RC799-869 Michaela Melde Tanja M. Müller Ines Schneider Carol-Immanuel Geppert Laura Mühl Laura Besendorf Clarissa Allner Emily Becker Imke Atreya Francesco Vitali Raja Atreya Markus F. Neurath Sebastian Zundler α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis |
| description |
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 in vitro . 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. |
| format |
article |
| author |
Michaela Melde Tanja M. Müller Ines Schneider Carol-Immanuel Geppert Laura Mühl Laura Besendorf Clarissa Allner Emily Becker Imke Atreya Francesco Vitali Raja Atreya Markus F. Neurath Sebastian Zundler |
| author_facet |
Michaela Melde Tanja M. Müller Ines Schneider Carol-Immanuel Geppert Laura Mühl Laura Besendorf Clarissa Allner Emily Becker Imke Atreya Francesco Vitali Raja Atreya Markus F. Neurath Sebastian Zundler |
| author_sort |
Michaela Melde |
| title |
α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis |
| title_short |
α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis |
| title_full |
α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis |
| title_fullStr |
α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis |
| title_full_unstemmed |
α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis |
| title_sort |
α4β7 integrin-dependent adhesion of t cells to madcam-1 is blocked by vedolizumab in patients with chronic refractory pouchitis |
| publisher |
SAGE Publishing |
| publishDate |
2021 |
| url |
https://doaj.org/article/66d7a961a1bc4e629574dec05f820ce5 |
| work_keys_str_mv |
AT michaelamelde a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT tanjammuller a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT inesschneider a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT carolimmanuelgeppert a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT lauramuhl a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT laurabesendorf a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT clarissaallner a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT emilybecker a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT imkeatreya a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT francescovitali a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT rajaatreya a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT markusfneurath a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis AT sebastianzundler a4b7integrindependentadhesionoftcellstomadcam1isblockedbyvedolizumabinpatientswithchronicrefractorypouchitis |
| _version_ |
1718403989111832576 |