Artículo
LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
Autor/es | Cruz, David
Rodríguez-Romanos, Rocío González-Bartulos, Marta García-Cadenas, Irene de la Cámara, Rafael Heras, Inmaculada Pérez Simón, José Antonio Gallardo, David |
Departamento | Universidad de Sevilla. Instituto de Biomedicina de Sevilla (IBIS) Universidad de Sevilla. Departamento de Medicina |
Fecha de publicación | 2023 |
Fecha de depósito | 2024-02-06 |
Publicado en |
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Resumen | 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 ... 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 |
Agencias financiadoras | Instituto de Salud Carlos III |
Identificador del proyecto | PI17/00815
PI20/ 01353 |
Cita | Cruz, D., Rodríguez-Romanos, R., González-Bartulos, M., García-Cadenas, I., de la Cámara, R., Heras, I.,...,Gallardo, D. (2023). LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors. Frontiers In Immunology, 14, 1066393. https://doi.org/10.3389/fimmu.2023.1066393. |
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