Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation

Rechazo agudo; Genética; Inmunobiología

Detalles Bibliográficos
Autores: Crespo Gimeno, Elena Isabel, Vidal-Alabró, Anna, Fontova, Pere, Stein, Maik, Mocka, Sonila, Meneghini. Maria Antonia Emilia, Torija Recasens, Alba, Moreso Mateos, Francesc, Bestard Matamoros, Oriol, Donadeu Casassas, Laura, Jouve, Thomas
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:11351/8204
Acceso en línea:https://hdl.handle.net/11351/8204
Access Level:acceso abierto
Palabra clave:Ronyons - Trasplantació
Cèl·lules B - Immunologia
Polimorfisme genètic
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Renal Replacement Therapy::Kidney Transplantation
ANATOMY::Cells::Antibody-Producing Cells::B-Lymphocytes
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::polimorfismo genético::polimorfismo de nucleótido único
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento de reemplazo renal::trasplante de riñón
ANATOMÍA::células::células productoras de anticuerpos::linfocitos B
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oai_identifier_str oai:recercat.cat:11351/8204
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
title Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
spellingShingle Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
Crespo Gimeno, Elena Isabel
Ronyons - Trasplantació
Cèl·lules B - Immunologia
Polimorfisme genètic
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Renal Replacement Therapy::Kidney Transplantation
ANATOMY::Cells::Antibody-Producing Cells::B-Lymphocytes
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::polimorfismo genético::polimorfismo de nucleótido único
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento de reemplazo renal::trasplante de riñón
ANATOMÍA::células::células productoras de anticuerpos::linfocitos B
title_short Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
title_full Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
title_fullStr Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
title_full_unstemmed Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
title_sort Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney Transplantation
dc.creator.none.fl_str_mv Crespo Gimeno, Elena Isabel
Vidal-Alabró, Anna
Fontova, Pere
Stein, Maik
Mocka, Sonila
Meneghini. Maria Antonia Emilia
Torija Recasens, Alba
Moreso Mateos, Francesc
Bestard Matamoros, Oriol
Donadeu Casassas, Laura
Jouve, Thomas
author Crespo Gimeno, Elena Isabel
author_facet Crespo Gimeno, Elena Isabel
Vidal-Alabró, Anna
Fontova, Pere
Stein, Maik
Mocka, Sonila
Meneghini. Maria Antonia Emilia
Torija Recasens, Alba
Moreso Mateos, Francesc
Bestard Matamoros, Oriol
Donadeu Casassas, Laura
Jouve, Thomas
author_role author
author2 Vidal-Alabró, Anna
Fontova, Pere
Stein, Maik
Mocka, Sonila
Meneghini. Maria Antonia Emilia
Torija Recasens, Alba
Moreso Mateos, Francesc
Bestard Matamoros, Oriol
Donadeu Casassas, Laura
Jouve, Thomas
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Institut Català de la Salut
[Crespo E, Torija A, Donadeu L] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Vidal-Alabró A, Fontova P, Mocka S] Experimental Nephrology and Transplantation Laboratory, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain. [Jouve T] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Faculty of Health, Université Grenoble Alpes, Grenoble, France. Institute for Advanced Biosciences, INSERM 1209, CNRS 5309, Grenoble, France. [Stein M] Berlin Center for Advanced Therapies (BeCAT), Berlin, Germany. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Berlin Institute of Health (BIH), Berlin, Germany. [Meneghini M, Bestard O] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Trasplantament Renal, Servei de Nefrologia, Vall d’Hebron Hospital, Barcelona, Spain. [Moreso F] Unitat de Trasplantament Renal, Servei de Nefrologia, Vall d’Hebron Hospital, Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
dc.subject.none.fl_str_mv Ronyons - Trasplantació
Cèl·lules B - Immunologia
Polimorfisme genètic
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Renal Replacement Therapy::Kidney Transplantation
ANATOMY::Cells::Antibody-Producing Cells::B-Lymphocytes
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::polimorfismo genético::polimorfismo de nucleótido único
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento de reemplazo renal::trasplante de riñón
ANATOMÍA::células::células productoras de anticuerpos::linfocitos B
topic Ronyons - Trasplantació
Cèl·lules B - Immunologia
Polimorfisme genètic
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single Nucleotide
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Renal Replacement Therapy::Kidney Transplantation
ANATOMY::Cells::Antibody-Producing Cells::B-Lymphocytes
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::polimorfismo genético::polimorfismo de nucleótido único
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento de reemplazo renal::trasplante de riñón
ANATOMÍA::células::células productoras de anticuerpos::linfocitos B
description Rechazo agudo; Genética; Inmunobiología
publishDate 2022
dc.date.none.fl_str_mv 2022
2022
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/11351/8204
url https://hdl.handle.net/11351/8204
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Frontiers in Immunology;13
https://doi.org/10.3389/fimmu.2022.869554
dc.rights.none.fl_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv Scientia
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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spelling Tacrolimus CYP3A Single-Nucleotide Polymorphisms and Preformed T- and B-Cell Alloimmune Memory Improve Current Pretransplant Rejection-Risk Stratification in Kidney TransplantationCrespo Gimeno, Elena IsabelVidal-Alabró, AnnaFontova, PereStein, MaikMocka, SonilaMeneghini. Maria Antonia EmiliaTorija Recasens, AlbaMoreso Mateos, FrancescBestard Matamoros, OriolDonadeu Casassas, LauraJouve, ThomasRonyons - TrasplantacióCèl·lules B - ImmunologiaPolimorfisme genèticPHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Polymorphism, Genetic::Polymorphism, Single NucleotideANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Therapeutics::Renal Replacement Therapy::Kidney TransplantationANATOMY::Cells::Antibody-Producing Cells::B-LymphocytesFENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::polimorfismo genético::polimorfismo de nucleótido únicoTÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::terapéutica::tratamiento de reemplazo renal::trasplante de riñónANATOMÍA::células::células productoras de anticuerpos::linfocitos BRechazo agudo; Genética; InmunobiologíaRebuig agut; Genètica; ImmunobiologiaAcute rejection; Genetics; ImmunobiologyAchieving fast immunosuppression blood exposure after kidney transplantation is key to abrogating both preformed and de novo anti-donor humoral and cellular alloresponses. However, while tacrolimus (TAC) is the cornerstone immunosuppressant inhibiting adaptive alloimmunity, its blood exposure is directly impacted by different single-nucleotide polymorphisms (SNPs) in CYP3A TAC-metabolizing enzymes. Here, we investigated how functional TAC-CYP3A genetic variants (CYP3A4*22/CYP3A5*3) influence the main baseline clinical and immunological risk factors of biopsy-proven acute rejection (BPAR) by means of preformed donor-specific antibodies (DSAs) and donor-specific alloreactive T cells (DSTs) in a large European cohort of 447 kidney transplants receiving TAC-based immunosuppression. A total of 70 (15.7%) patients developed BPAR. Preformed DSAs and DSTs were observed in 12 (2.7%) and 227 (50.8%) patients, respectively. According to the different CYP3A4*22 and CYP3A5*3 functional allele variants, we found 4 differential new clusters impacting fasting TAC exposure after transplantation; 7 (1.6%) were classified as high metabolizers 1 (HM1), 71 (15.9%) as HM2, 324 (72.5%) as intermediate (IM), and 45 (10.1%) as poor metabolizers (PM1). HM1/2 showed significantly lower TAC trough levels and higher dose requirements than IM and PM (p < 0.001) and more frequently showed TAC underexposure (<5 ng/ml). Multivariate Cox regression analyses revealed that CYP3A HM1 and IM pharmacogenetic phenotypes (hazard ratio (HR) 12.566, 95% CI 1.99-79.36, p = 0.007, and HR 4.532, 95% CI 1.10-18.60, p = 0.036, respectively), preformed DSTs (HR 3.482, 95% CI 1.99-6.08, p < 0.001), DSAs (HR 4.421, 95% CI 1.63-11.98, p = 0.003), and delayed graft function (DGF) (HR 2.023, 95% CI 1.22-3.36, p = 0.006) independently predicted BPAR. Notably, a significant interaction between T-cell depletion and TAC underexposure was observed, showing a reduction of the BPAR risk (HR 0.264, 95% CI 0.08-0.92, p = 0.037). Such variables except for DSAs displayed a higher predictive risk for the development of T cell-mediated rejection (TCMR). Refinement of pretransplant monitoring by incorporating TAC CYP3A SNPs with preformed DSAs as well as DSTs may improve current rejection-risk stratification and help induction treatment decision-making.This work was supported by the Instituto de Salud Carlos III (ISCIII) (grant numbers PI16/01321, PI19/01710, and PI18/P1740) (co-funded by European Regional Development Fund, ERDF, a way to build Europe). Also, this work was partly supported by the SLT002/16/00183 grant, from the Department of Health of the Generalitat de Catalunya by the call “Acció instrumental de programes de recerca orientats en l’àmbit de la recerca i la innovació en salut.” The authors thank the Research Centers of Catalonia (CERCA) Programme/Generalitat de Catalunya for institutional support. OB was awarded an intensification grant from the “Instituto de Salud Carlos III” [NT19/00051].Frontiers MediaInstitut Català de la Salut[Crespo E, Torija A, Donadeu L] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. [Vidal-Alabró A, Fontova P, Mocka S] Experimental Nephrology and Transplantation Laboratory, Instituto de Investigación Biomédica de Bellvitge (IDIBELL), Barcelona, Spain. [Jouve T] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Faculty of Health, Université Grenoble Alpes, Grenoble, France. Institute for Advanced Biosciences, INSERM 1209, CNRS 5309, Grenoble, France. [Stein M] Berlin Center for Advanced Therapies (BeCAT), Berlin, Germany. Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Berlin Institute of Health (BIH), Berlin, Germany. [Meneghini M, Bestard O] Laboratori de Nefrologia i Trasplantament Renal, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain. Unitat de Trasplantament Renal, Servei de Nefrologia, Vall d’Hebron Hospital, Barcelona, Spain. [Moreso F] Unitat de Trasplantament Renal, Servei de Nefrologia, Vall d’Hebron Hospital, Barcelona, SpainVall d'Hebron Barcelona Hospital Campus202220222022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/11351/8204Scientiareponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésFrontiers in Immunology;13https://doi.org/10.3389/fimmu.2022.869554Attribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:11351/82042026-05-29T05:05:01Z
score 15,81155

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