Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation

Antibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR d...

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Autores: Roufosse, Candice, Becker, Jan Ulrich, Rabant, Marion, Seron, Daniel, Bellini, Maria Irene, Böhmig, Georg A., Budde, Klemens, Diekmann, Fritz, Glotz, Denis, Hilbrands, Luuk, Loupy, Alexandre, Oberbauer, Rainer, Pengel, Liset, Schneeberger, Stefan, Naesens, Maarten
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/206275
Acceso en línea:https://hdl.handle.net/2445/206275
Access Level:acceso abierto
Palabra clave:Antígens HLA
Rebuig (Biologia)
HLA histocompatibility antigens
Graft rejection
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spelling Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney TransplantationRoufosse, CandiceBecker, Jan UlrichRabant, MarionSeron, DanielBellini, Maria IreneBöhmig, Georg A.Budde, KlemensDiekmann, FritzGlotz, DenisHilbrands, LuukLoupy, AlexandreOberbauer, RainerPengel, LisetSchneeberger, StefanNaesens, MaartenAntígens HLARebuig (Biologia)HLA histocompatibility antigensGraft rejectionAntibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR definition have made it difficult to compare data and evaluate associations between AMR and graft outcome. The present paper was developed following a Broad Scientific Advice request from the European Society for Organ Transplantation (ESOT) to the European Medicines Agency (EMA), which explored whether updating guidelines on clinical trial endpoints would encourage innovations in kidney transplantation research. ESOT considers that an AMR diagnosis must be based on a combination of histopathological factors and presence of donor-specific HLA antibodies in the recipient. Evidence for associations between individual features of AMR and impaired graft outcome is noted for microvascular inflammation scores ≥2 and glomerular basement membrane splitting of >10% of the entire tuft in the most severely affected glomerulus. Together, these should form the basis for AMR-related endpoints in clinical trials of kidney transplantation, although modifications and restrictions to the Banff diagnostic definition of AMR are proposed for this purpose. The EMA provided recommendations based on this Broad Scientific Advice request in December 2020; further discussion, and consensus on the restricted definition of the AMR endpoint, is required.Copyright © 2022 Roufosse, Becker, Rabant, Seron, Bellini, Böhmig, Budde, Diekmann, Glotz, Hilbrands, Loupy, Oberbauer, Pengel, Schneeberger and Naesens.2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/206275Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/ti.2022.10140TRANSPLANT INTERNATIONAL, 2022, vol. 35, p. 10140https://doi.org/10.3389/ti.2022.10140cc by (c) Roufosse, C. et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2062752026-05-27T06:46:51Z
dc.title.none.fl_str_mv Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
title Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
spellingShingle Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
Roufosse, Candice
Antígens HLA
Rebuig (Biologia)
HLA histocompatibility antigens
Graft rejection
title_short Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
title_full Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
title_fullStr Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
title_full_unstemmed Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
title_sort Proposed Definitions of Antibody-Mediated Rejection for Use as a Clinical Trial Endpoint in Kidney Transplantation
dc.creator.none.fl_str_mv Roufosse, Candice
Becker, Jan Ulrich
Rabant, Marion
Seron, Daniel
Bellini, Maria Irene
Böhmig, Georg A.
Budde, Klemens
Diekmann, Fritz
Glotz, Denis
Hilbrands, Luuk
Loupy, Alexandre
Oberbauer, Rainer
Pengel, Liset
Schneeberger, Stefan
Naesens, Maarten
author Roufosse, Candice
author_facet Roufosse, Candice
Becker, Jan Ulrich
Rabant, Marion
Seron, Daniel
Bellini, Maria Irene
Böhmig, Georg A.
Budde, Klemens
Diekmann, Fritz
Glotz, Denis
Hilbrands, Luuk
Loupy, Alexandre
Oberbauer, Rainer
Pengel, Liset
Schneeberger, Stefan
Naesens, Maarten
author_role author
author2 Becker, Jan Ulrich
Rabant, Marion
Seron, Daniel
Bellini, Maria Irene
Böhmig, Georg A.
Budde, Klemens
Diekmann, Fritz
Glotz, Denis
Hilbrands, Luuk
Loupy, Alexandre
Oberbauer, Rainer
Pengel, Liset
Schneeberger, Stefan
Naesens, Maarten
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Antígens HLA
Rebuig (Biologia)
HLA histocompatibility antigens
Graft rejection
topic Antígens HLA
Rebuig (Biologia)
HLA histocompatibility antigens
Graft rejection
description Antibody-mediated rejection (AMR) is caused by antibodies that recognize donor human leukocyte antigen (HLA) or other targets. As knowledge of AMR pathophysiology has increased, a combination of factors is necessary to confirm the diagnosis and phenotype. However, frequent modifications to the AMR definition have made it difficult to compare data and evaluate associations between AMR and graft outcome. The present paper was developed following a Broad Scientific Advice request from the European Society for Organ Transplantation (ESOT) to the European Medicines Agency (EMA), which explored whether updating guidelines on clinical trial endpoints would encourage innovations in kidney transplantation research. ESOT considers that an AMR diagnosis must be based on a combination of histopathological factors and presence of donor-specific HLA antibodies in the recipient. Evidence for associations between individual features of AMR and impaired graft outcome is noted for microvascular inflammation scores ≥2 and glomerular basement membrane splitting of >10% of the entire tuft in the most severely affected glomerulus. Together, these should form the basis for AMR-related endpoints in clinical trials of kidney transplantation, although modifications and restrictions to the Banff diagnostic definition of AMR are proposed for this purpose. The EMA provided recommendations based on this Broad Scientific Advice request in December 2020; further discussion, and consensus on the restricted definition of the AMR endpoint, is required.Copyright © 2022 Roufosse, Becker, Rabant, Seron, Bellini, Böhmig, Budde, Diekmann, Glotz, Hilbrands, Loupy, Oberbauer, Pengel, Schneeberger and Naesens.
publishDate 2022
dc.date.none.fl_str_mv 2022
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/206275
url https://hdl.handle.net/2445/206275
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/10.3389/ti.2022.10140
TRANSPLANT INTERNATIONAL, 2022, vol. 35, p. 10140
https://doi.org/10.3389/ti.2022.10140
dc.rights.none.fl_str_mv cc by (c) Roufosse, C. et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Roufosse, C. et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,301603

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