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...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p15676 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=15676 https://www.scopus.com/inward/record.uri?eid=2-s2.0-85147390494&doi=10.3389%2ffimmu.2023.1066393&partnerID=40&md5=f52184a5ddc68f269793d5d9d456ecaf |
| Access Level: | acceso abierto |
| Palabra clave: | adverse event allotransplantation genetics genotype graft versus host reaction hematopoietic stem cell transplantation human lymphocyte activation sibling Genotype Graft vs Host Disease Hematopoietic Stem Cell Transplantation Humans Lymphocyte Activation Siblings Transplantation, Homologous |
| Sumario: | 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 transplant-related 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. Copyright © 2023 Cruz, Rodríguez-Romanos, González-Bartulos, García-Cadenas, de la Cámara, Heras, Buño, Santos, Lloveras, Velarde, Tuset, Martínez, González, Sanz, Ferrá, Sampol, Coll, Pérez-Simón, López-Jiménez, Jurado and Gallardo. |
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