B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization
Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could...
| Autores: | , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Fecha de publicación: | 2021 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:252157 |
| Acceso en línea: | https://ddd.uab.cat/record/252157 https://dx.doi.org/urn:doi:10.3389/fmed.2021.781239 |
| Access Level: | acceso abierto |
| Palabra clave: | B cells Kidney transplantation Desensitization HLA-incompatibility Extracellular vesicles (EV) Exosomes Plasma cells |
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B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant DesensitizationCucchiari, David|||0000-0002-7594-1070Tubita, ValeriaRovira, Jordi|||0000-0001-8737-5005Ramirez-Bajo, Maria J..Banon-Maneus, ElisendaLazo-Rodriguez, MartaHierro-Garcia, NataliaBorràs i Serres, Francesc Enric|||0000-0003-4038-1912Ventura-Aguiar, Pedro|||0000-0003-3381-7503Piñeiro, Gastón Julio|||0000-0003-3806-4731Martorell Montserrat, Jaume|||0000-0001-9031-0042Peri, LluísMusquera, MireiaHertig, AlexandreOppenheimer, Federico|||0000-0002-1117-831XCampistol, Josep M..Diekmann, Fritz|||0000-0001-6199-3016Revuelta, Ignacio|||0000-0002-3584-4516B cellsKidney transplantationDesensitizationHLA-incompatibilityExtracellular vesicles (EV)ExosomesPlasma cellsBackground: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs). Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization. Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable. Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting.Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/252157https://dx.doi.org/urn:doi:10.3389/fmed.2021.781239reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengMinisterio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00115Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0009/0023Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1331open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2521572026-06-06T12:50:31Z |
| dc.title.none.fl_str_mv |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization |
| title |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization |
| spellingShingle |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization Cucchiari, David|||0000-0002-7594-1070 B cells Kidney transplantation Desensitization HLA-incompatibility Extracellular vesicles (EV) Exosomes Plasma cells |
| title_short |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization |
| title_full |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization |
| title_fullStr |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization |
| title_full_unstemmed |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization |
| title_sort |
B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization |
| dc.creator.none.fl_str_mv |
Cucchiari, David|||0000-0002-7594-1070 Tubita, Valeria Rovira, Jordi|||0000-0001-8737-5005 Ramirez-Bajo, Maria J.. Banon-Maneus, Elisenda Lazo-Rodriguez, Marta Hierro-Garcia, Natalia Borràs i Serres, Francesc Enric|||0000-0003-4038-1912 Ventura-Aguiar, Pedro|||0000-0003-3381-7503 Piñeiro, Gastón Julio|||0000-0003-3806-4731 Martorell Montserrat, Jaume|||0000-0001-9031-0042 Peri, Lluís Musquera, Mireia Hertig, Alexandre Oppenheimer, Federico|||0000-0002-1117-831X Campistol, Josep M.. Diekmann, Fritz|||0000-0001-6199-3016 Revuelta, Ignacio|||0000-0002-3584-4516 |
| author |
Cucchiari, David|||0000-0002-7594-1070 |
| author_facet |
Cucchiari, David|||0000-0002-7594-1070 Tubita, Valeria Rovira, Jordi|||0000-0001-8737-5005 Ramirez-Bajo, Maria J.. Banon-Maneus, Elisenda Lazo-Rodriguez, Marta Hierro-Garcia, Natalia Borràs i Serres, Francesc Enric|||0000-0003-4038-1912 Ventura-Aguiar, Pedro|||0000-0003-3381-7503 Piñeiro, Gastón Julio|||0000-0003-3806-4731 Martorell Montserrat, Jaume|||0000-0001-9031-0042 Peri, Lluís Musquera, Mireia Hertig, Alexandre Oppenheimer, Federico|||0000-0002-1117-831X Campistol, Josep M.. Diekmann, Fritz|||0000-0001-6199-3016 Revuelta, Ignacio|||0000-0002-3584-4516 |
| author_role |
author |
| author2 |
Tubita, Valeria Rovira, Jordi|||0000-0001-8737-5005 Ramirez-Bajo, Maria J.. Banon-Maneus, Elisenda Lazo-Rodriguez, Marta Hierro-Garcia, Natalia Borràs i Serres, Francesc Enric|||0000-0003-4038-1912 Ventura-Aguiar, Pedro|||0000-0003-3381-7503 Piñeiro, Gastón Julio|||0000-0003-3806-4731 Martorell Montserrat, Jaume|||0000-0001-9031-0042 Peri, Lluís Musquera, Mireia Hertig, Alexandre Oppenheimer, Federico|||0000-0002-1117-831X Campistol, Josep M.. Diekmann, Fritz|||0000-0001-6199-3016 Revuelta, Ignacio|||0000-0002-3584-4516 |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia |
| dc.subject.none.fl_str_mv |
B cells Kidney transplantation Desensitization HLA-incompatibility Extracellular vesicles (EV) Exosomes Plasma cells |
| topic |
B cells Kidney transplantation Desensitization HLA-incompatibility Extracellular vesicles (EV) Exosomes Plasma cells |
| description |
Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs). Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization. Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable. Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2 2021-01-01 2021 2021-01-01 |
| dc.type.none.fl_str_mv |
Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85 |
| dc.type.openaire.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| dc.identifier.none.fl_str_mv |
https://ddd.uab.cat/record/252157 https://dx.doi.org/urn:doi:10.3389/fmed.2021.781239 |
| url |
https://ddd.uab.cat/record/252157 https://dx.doi.org/urn:doi:10.3389/fmed.2021.781239 |
| dc.language.none.fl_str_mv |
Inglés eng |
| language_invalid_str_mv |
Inglés |
| language |
eng |
| dc.relation.none.fl_str_mv |
Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 PI16/00115 Ministerio de Economía y Competitividad https://doi.org/10.13039/501100003329 RD16/0009/0023 Agència de Gestió d'Ajuts Universitaris i de Recerca https://doi.org/10.13039/501100003030 2017/SGR-1331 |
| dc.rights.none.fl_str_mv |
open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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info:eu-repo/semantics/openAccess |
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open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/ |
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openAccess |
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application/pdf |
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reponame:Dipòsit Digital de Documents de la UAB instname:Universitat Autònoma de Barcelona |
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Universitat Autònoma de Barcelona |
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Dipòsit Digital de Documents de la UAB |
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