Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis
Background and Aims:Vedolizumab is an anti-α4β7 antibody approved for the treatment of ulcerative colitis [UC]. Although it is assumed that vedolizumab blocks intestinal homing of lymphocytes, its effects on different intestinal cell populations are not fully stablished. In order to establish the un...
| Autores: | , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/177748 |
| Acceso en línea: | https://hdl.handle.net/2445/177748 |
| Access Level: | acceso abierto |
| Palabra clave: | Colitis ulcerosa Malalties de l'aparell digestiu Gastroenterologia Ulcerative colitis Digestive system diseases Gastroenterology |
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Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitisVeny Alvarez-Ossorio, MarisolGarrido Trigo, AlbaCorraliza Márquez, Ana MariaMasamunt, Maria CarmeBassolas Molina, HelenaEsteller Viñal, MiriamArroyes, MontserratTristán, EvaFernández Clotet, AgnèsOrdas, IngridRicart, ElenaEsteve i Comas, MariaPanés Díaz, JuliàSalas Martínez, AzucenaColitis ulcerosaMalalties de l'aparell digestiuGastroenterologiaUlcerative colitisDigestive system diseasesGastroenterologyBackground and Aims:Vedolizumab is an anti-α4β7 antibody approved for the treatment of ulcerative colitis [UC]. Although it is assumed that vedolizumab blocks intestinal homing of lymphocytes, its effects on different intestinal cell populations are not fully stablished. In order to establish the unique mechanisms of action of vedolizumab in UC patients, we compared its effects to those induced by anti-tumour necrosis factor [TNF]. Methods:patients with active UC [endoscopic Mayo score >1] starting vedolizumab [n = 33] or anti-TNF [n = 45] and controls [n = 22] were included. Colon biopsies [at weeks 0, 14 and 46] and blood samples [at weeks 0, 2, 6, 14, 30 and 46] were used for cell phenotyping, transcriptional analysis [qPCR], and to measure receptor occupancy. Results:Vedolizumab, in contrast to anti-TNF, significantly reduced the proportion of α4β7+ cells within intestinal T subsets while preserving the percentage of α4β7+ plasma cells. The marked decrease in α4β7 did not change the percentage of colonic αEβ7+ cells [at 46 weeks]. Both vedolizumab and anti-TNF significantly downregulated inflammation-related genes in the colon of responders [Mayo score < 2]. Moreover, both treatments significantly decreased the percentage of intestinal, but not blood, total lymphocytes [T and plasma cells], as well as the proportion of α4β1+ cells within intestinal T lymphocytes. Conclusions:Our data show that while vedolizumab and anti-TNF block two unrelated targets, they induce remarkably similar effects. On the other hand, vedolizumab's unique mechanism of action relies on blocking intestinal trafficking of α4β7 T cells, despite effectively binding to B and plasma cells that express α4β7.Elsevier2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/177748Articles publicats en revistes (Medicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1093/ecco-jcc/jjaa178Journal of Crohn's and Colitis, 2021, vol. 15, num. 3, p. 441-452https://doi.org/10.1093/ecco-jcc/jjaa178cc-by-nc-nd (c)Veny Alvarez-Ossorio, Marisol et al., 2021http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1777482026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis |
| title |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis |
| spellingShingle |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis Veny Alvarez-Ossorio, Marisol Colitis ulcerosa Malalties de l'aparell digestiu Gastroenterologia Ulcerative colitis Digestive system diseases Gastroenterology |
| title_short |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis |
| title_full |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis |
| title_fullStr |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis |
| title_full_unstemmed |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis |
| title_sort |
Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis |
| dc.creator.none.fl_str_mv |
Veny Alvarez-Ossorio, Marisol Garrido Trigo, Alba Corraliza Márquez, Ana Maria Masamunt, Maria Carme Bassolas Molina, Helena Esteller Viñal, Miriam Arroyes, Montserrat Tristán, Eva Fernández Clotet, Agnès Ordas, Ingrid Ricart, Elena Esteve i Comas, Maria Panés Díaz, Julià Salas Martínez, Azucena |
| author |
Veny Alvarez-Ossorio, Marisol |
| author_facet |
Veny Alvarez-Ossorio, Marisol Garrido Trigo, Alba Corraliza Márquez, Ana Maria Masamunt, Maria Carme Bassolas Molina, Helena Esteller Viñal, Miriam Arroyes, Montserrat Tristán, Eva Fernández Clotet, Agnès Ordas, Ingrid Ricart, Elena Esteve i Comas, Maria Panés Díaz, Julià Salas Martínez, Azucena |
| author_role |
author |
| author2 |
Garrido Trigo, Alba Corraliza Márquez, Ana Maria Masamunt, Maria Carme Bassolas Molina, Helena Esteller Viñal, Miriam Arroyes, Montserrat Tristán, Eva Fernández Clotet, Agnès Ordas, Ingrid Ricart, Elena Esteve i Comas, Maria Panés Díaz, Julià Salas Martínez, Azucena |
| author2_role |
author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Colitis ulcerosa Malalties de l'aparell digestiu Gastroenterologia Ulcerative colitis Digestive system diseases Gastroenterology |
| topic |
Colitis ulcerosa Malalties de l'aparell digestiu Gastroenterologia Ulcerative colitis Digestive system diseases Gastroenterology |
| description |
Background and Aims:Vedolizumab is an anti-α4β7 antibody approved for the treatment of ulcerative colitis [UC]. Although it is assumed that vedolizumab blocks intestinal homing of lymphocytes, its effects on different intestinal cell populations are not fully stablished. In order to establish the unique mechanisms of action of vedolizumab in UC patients, we compared its effects to those induced by anti-tumour necrosis factor [TNF]. Methods:patients with active UC [endoscopic Mayo score >1] starting vedolizumab [n = 33] or anti-TNF [n = 45] and controls [n = 22] were included. Colon biopsies [at weeks 0, 14 and 46] and blood samples [at weeks 0, 2, 6, 14, 30 and 46] were used for cell phenotyping, transcriptional analysis [qPCR], and to measure receptor occupancy. Results:Vedolizumab, in contrast to anti-TNF, significantly reduced the proportion of α4β7+ cells within intestinal T subsets while preserving the percentage of α4β7+ plasma cells. The marked decrease in α4β7 did not change the percentage of colonic αEβ7+ cells [at 46 weeks]. Both vedolizumab and anti-TNF significantly downregulated inflammation-related genes in the colon of responders [Mayo score < 2]. Moreover, both treatments significantly decreased the percentage of intestinal, but not blood, total lymphocytes [T and plasma cells], as well as the proportion of α4β1+ cells within intestinal T lymphocytes. Conclusions:Our data show that while vedolizumab and anti-TNF block two unrelated targets, they induce remarkably similar effects. On the other hand, vedolizumab's unique mechanism of action relies on blocking intestinal trafficking of α4β7 T cells, despite effectively binding to B and plasma cells that express α4β7. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion |
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article |
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acceptedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/177748 |
| url |
https://hdl.handle.net/2445/177748 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1093/ecco-jcc/jjaa178 Journal of Crohn's and Colitis, 2021, vol. 15, num. 3, p. 441-452 https://doi.org/10.1093/ecco-jcc/jjaa178 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c)Veny Alvarez-Ossorio, Marisol et al., 2021 http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c)Veny Alvarez-Ossorio, Marisol et al., 2021 http://creativecommons.org/licenses/by-nc/3.0/es/ |
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openAccess |
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application/pdf |
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Elsevier |
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Elsevier |
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Articles publicats en revistes (Medicina) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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