LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

Introduction: The association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity a...

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Autores: Cruz, David, Rodríguez-Romanos, Rocío, González-Bartulos, Marta, García-Cadenas, Irene, de la Cámara, Rafael, Heras, Inmaculada, Pérez Simón, José Antonio, Gallardo, David
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/154738
Acceso en línea:https://hdl.handle.net/11441/154738
https://doi.org/10.3389/fimmu.2023.1066393
Access Level:acceso abierto
Palabra clave:Lymphocyte activation gene 3
Graft-versus-host disease
Allogeneic transplant
Immune response
Checkpoint molecules
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spelling LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donorsCruz, DavidRodríguez-Romanos, RocíoGonzález-Bartulos, MartaGarcía-Cadenas, Irenede la Cámara, RafaelHeras, InmaculadaPérez Simón, José AntonioGallardo, DavidLymphocyte activation gene 3Graft-versus-host diseaseAllogeneic transplantImmune responseCheckpoint moleculesIntroduction: The association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule. Methods: To determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C>T polymorphism was genotyped in donors. Results: We detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplantrelated mortality (TRM) (p< 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS. Discussion: We conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warrantedFrontiers Media S.A.Instituto de Biomedicina de Sevilla (IBIS)MedicinaInstituto de Salud Carlos III2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/154738https://doi.org/10.3389/fimmu.2023.1066393reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésFrontiers In Immunology, 14, 1066393.PI17/00815PI20/ 01353https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1066393/fullinfo:eu-repo/semantics/openAccessoai:idus.us.es:11441/1547382026-06-17T12:51:07Z
dc.title.none.fl_str_mv LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
spellingShingle LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
Cruz, David
Lymphocyte activation gene 3
Graft-versus-host disease
Allogeneic transplant
Immune response
Checkpoint molecules
title_short LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_full LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_fullStr LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_full_unstemmed LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
title_sort LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
dc.creator.none.fl_str_mv Cruz, David
Rodríguez-Romanos, Rocío
González-Bartulos, Marta
García-Cadenas, Irene
de la Cámara, Rafael
Heras, Inmaculada
Pérez Simón, José Antonio
Gallardo, David
author Cruz, David
author_facet Cruz, David
Rodríguez-Romanos, Rocío
González-Bartulos, Marta
García-Cadenas, Irene
de la Cámara, Rafael
Heras, Inmaculada
Pérez Simón, José Antonio
Gallardo, David
author_role author
author2 Rodríguez-Romanos, Rocío
González-Bartulos, Marta
García-Cadenas, Irene
de la Cámara, Rafael
Heras, Inmaculada
Pérez Simón, José Antonio
Gallardo, David
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Instituto de Biomedicina de Sevilla (IBIS)
Medicina
Instituto de Salud Carlos III
dc.subject.none.fl_str_mv Lymphocyte activation gene 3
Graft-versus-host disease
Allogeneic transplant
Immune response
Checkpoint molecules
topic Lymphocyte activation gene 3
Graft-versus-host disease
Allogeneic transplant
Immune response
Checkpoint molecules
description Introduction: The association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule. Methods: To determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C>T polymorphism was genotyped in donors. Results: We detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplantrelated mortality (TRM) (p< 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS. Discussion: We conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warranted
publishDate 2023
dc.date.none.fl_str_mv 2023
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/11441/154738
https://doi.org/10.3389/fimmu.2023.1066393
url https://hdl.handle.net/11441/154738
https://doi.org/10.3389/fimmu.2023.1066393
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Frontiers In Immunology, 14, 1066393.
PI17/00815
PI20/ 01353
https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1066393/full
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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