B Cell-Derived Extracellular Vesicles Reveal Residual B Cell Activity in Kidney Graft Recipients Undergoing Pre-Transplant Desensitization
Cucchiari, David (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Tubita, Valeria (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Rovira, Jordi (Red de Investigación Renal (REDINREN))
Ramirez-Bajo, Maria J.. (Red de Investigación Renal (REDINREN))
Banon-Maneus, Elisenda (Red de Investigación Renal (REDINREN))
Lazo-Rodriguez, Marta (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Hierro-Garcia, Natalia (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Borràs i Serres, Francesc Enric (Institut Germans Trias i Pujol)
Ventura-Aguiar, Pedro (Hospital Clínic i Provincial de Barcelona)
Piñeiro, Gastón J. (Hospital Clínic i Provincial de Barcelona)
Martorell Montserrat, Jaume (Hospital Clínic i Provincial de Barcelona)
Peri, Lluís (Hospital Clínic i Provincial de Barcelona)
Musquera, Mireia (Hospital Clínic i Provincial de Barcelona)
Hertig, Alexandre (Service de Néphrologie, Hôpital Foch)
Oppenheimer, Federico (Red de Investigación Renal (REDINREN))
Campistol, Josep M.. (Red de Investigación Renal (REDINREN))
Diekmann, Fritz (Red de Investigación Renal (REDINREN))
Revuelta, Ignacio (Red de Investigación Renal (REDINREN))
Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia

Date:	2021
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad PI16/00115 Ministerio de Economía y Competitividad RD16/0009/0023 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017-SGR-1331
Rights:	Aquest 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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	B cells ; Kidney transplantation ; Desensitization ; HLA-incompatibility ; Extracellular vesicles (EV) ; Exosomes ; Plasma cells
Published in:	Frontiers in Medicine, Vol. 8 (december 2021) , ISSN 2296-858X

DOI: 10.3389/fmed.2021.781239
PMID: 34977082

11 p, 2.2 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
Articles > Research articles
Articles > Published articles