On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes

Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor-recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed....

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Autores: Meneghini, Maria, Perona, Anna, Crespo Fernández, Elena, Bemelman, Frederike, Reinke, Petra, Viklicky, Ondrej, Giral, Magali, Palou, Eduard, Torija Recasens, Alba, Donadeu, Laura, Melilli, Edoardo, Zuñiga, Jose, Sefrin, Anett, Lachmann, Nils, Hu, Liu, Hruba, Petra, Guillot Gueguen, Cécile, Brouard, Sophie, Grinyó Boira, Josep M., Bestard Matamoros, Oriol
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:2445/190743
Acceso en línea:https://hdl.handle.net/2445/190743
Access Level:acceso abierto
Palabra clave:Trasplantament renal
Rebuig (Biologia)
Kidney transplantation
Graft rejection
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spelling On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomesMeneghini, MariaPerona, AnnaCrespo Fernández, ElenaBemelman, FrederikeReinke, PetraViklicky, OndrejGiral, MagaliPalou, EduardTorija Recasens, AlbaDonadeu, LauraMelilli, EdoardoZuñiga, JoseSefrin, AnettLachmann, NilsHu, LiuHruba, PetraGuillot Gueguen, CécileBrouard, SophieGrinyó Boira, Josep M.Bestard Matamoros, OriolTrasplantament renalRebuig (Biologia)Kidney transplantationGraft rejectionComplete and high-resolution (HR) HLA typing improves the accurate assessment of donor-recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing. De novo anti-HLA antibodies were assessed using solid-phase assays, and dnDSA were classified either (1) as per current clinical practice according to three-locus (A/B/DRB1) low-resolution (LR) typing, estimating donor HLA-C/DQ typing with frequency tables, or (2) according to complete six-locus HR typing. The impact on graft outcomes was compared between groups. According to LR HLA typing, 36 (15%) patients developed dnDSA (LR_dnDSA+). Twenty-nine out of 36 (80%) were confirmed to have dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7 (20%) did not (LR_dnDSA+/HR_dnDSA-). Out of 49 LR_dnDSA specificities, 34 (69%) were confirmed by HR typing whereas 15 (31%) LR specificities were not confirmed. LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to dnDSA- and LR_dnDSA+/HR_dnDSA- (logRank < 0.001), and higher risk of death-censored graft loss (logRank = 0.001). Both LR_dnDSA+ (HR: 3.51, 95% CI = 1.25-9.85) and LR_dnDSA+/HR_dnDSA+ (HR: 4.09, 95% CI = 1.45-11.54), but not LR_dnDSA+/HR_dnDSA- independently predicted graft loss. The implementation of HR HLA typing improves the characterization of biologically relevant de novo anti-HLA DSA and discriminates patients with poorer graft outcomes.Frontiers Media SA2022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/190743Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.3389/fimmu.2022.924825Frontiers in Immunology, 2022, vol. 13https://doi.org/10.3389/fimmu.2022.924825info:eu-repo/grantAgreement/EC/FP7/305147cc by (c) Meneghini, Maria et al., 2022http://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1907432026-05-27T06:46:51Z
dc.title.none.fl_str_mv On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
title On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
spellingShingle On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
Meneghini, Maria
Trasplantament renal
Rebuig (Biologia)
Kidney transplantation
Graft rejection
title_short On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
title_full On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
title_fullStr On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
title_full_unstemmed On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
title_sort On the clinical relevance of using complete high-resolution HLA typing for an accurate interpretation of posttransplant immune-mediated graft outcomes
dc.creator.none.fl_str_mv Meneghini, Maria
Perona, Anna
Crespo Fernández, Elena
Bemelman, Frederike
Reinke, Petra
Viklicky, Ondrej
Giral, Magali
Palou, Eduard
Torija Recasens, Alba
Donadeu, Laura
Melilli, Edoardo
Zuñiga, Jose
Sefrin, Anett
Lachmann, Nils
Hu, Liu
Hruba, Petra
Guillot Gueguen, Cécile
Brouard, Sophie
Grinyó Boira, Josep M.
Bestard Matamoros, Oriol
author Meneghini, Maria
author_facet Meneghini, Maria
Perona, Anna
Crespo Fernández, Elena
Bemelman, Frederike
Reinke, Petra
Viklicky, Ondrej
Giral, Magali
Palou, Eduard
Torija Recasens, Alba
Donadeu, Laura
Melilli, Edoardo
Zuñiga, Jose
Sefrin, Anett
Lachmann, Nils
Hu, Liu
Hruba, Petra
Guillot Gueguen, Cécile
Brouard, Sophie
Grinyó Boira, Josep M.
Bestard Matamoros, Oriol
author_role author
author2 Perona, Anna
Crespo Fernández, Elena
Bemelman, Frederike
Reinke, Petra
Viklicky, Ondrej
Giral, Magali
Palou, Eduard
Torija Recasens, Alba
Donadeu, Laura
Melilli, Edoardo
Zuñiga, Jose
Sefrin, Anett
Lachmann, Nils
Hu, Liu
Hruba, Petra
Guillot Gueguen, Cécile
Brouard, Sophie
Grinyó Boira, Josep M.
Bestard Matamoros, Oriol
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trasplantament renal
Rebuig (Biologia)
Kidney transplantation
Graft rejection
topic Trasplantament renal
Rebuig (Biologia)
Kidney transplantation
Graft rejection
description Complete and high-resolution (HR) HLA typing improves the accurate assessment of donor-recipient compatibility and pre-transplant donor-specific antibodies (DSA). However, the value of this information to identify de novo immune-mediated graft events and its impact on outcomes has not been assessed. In 241 donor/recipient kidney transplant pairs, DNA samples were re-evaluated for six-locus (A/B/C/DRB1/DQB1+A1/DPB1) HR HLA typing. De novo anti-HLA antibodies were assessed using solid-phase assays, and dnDSA were classified either (1) as per current clinical practice according to three-locus (A/B/DRB1) low-resolution (LR) typing, estimating donor HLA-C/DQ typing with frequency tables, or (2) according to complete six-locus HR typing. The impact on graft outcomes was compared between groups. According to LR HLA typing, 36 (15%) patients developed dnDSA (LR_dnDSA+). Twenty-nine out of 36 (80%) were confirmed to have dnDSA by HR typing (LR_dnDSA+/HR_dnDSA+), whereas 7 (20%) did not (LR_dnDSA+/HR_dnDSA-). Out of 49 LR_dnDSA specificities, 34 (69%) were confirmed by HR typing whereas 15 (31%) LR specificities were not confirmed. LR_dnDSA+/HR_dnDSA+ patients were at higher risk of ABMR as compared to dnDSA- and LR_dnDSA+/HR_dnDSA- (logRank < 0.001), and higher risk of death-censored graft loss (logRank = 0.001). Both LR_dnDSA+ (HR: 3.51, 95% CI = 1.25-9.85) and LR_dnDSA+/HR_dnDSA+ (HR: 4.09, 95% CI = 1.45-11.54), but not LR_dnDSA+/HR_dnDSA- independently predicted graft loss. The implementation of HR HLA typing improves the characterization of biologically relevant de novo anti-HLA DSA and discriminates patients with poorer graft outcomes.
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/2445/190743
url https://hdl.handle.net/2445/190743
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/fimmu.2022.924825
Frontiers in Immunology, 2022, vol. 13
https://doi.org/10.3389/fimmu.2022.924825
info:eu-repo/grantAgreement/EC/FP7/305147
dc.rights.none.fl_str_mv cc by (c) Meneghini, Maria et al., 2022
http://creativecommons.org/licenses/by/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by (c) Meneghini, Maria 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.publisher.none.fl_str_mv Frontiers Media SA
publisher.none.fl_str_mv Frontiers Media SA
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
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 15,300719

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