LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors
Cruz, David (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Rodríguez-Romanos, Rocío (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
González-Bartulos, Marta (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Garcia Cadenas, Irene (Institut d'Investigació Biomèdica Sant Pau)
de la Camara, Rafael (Hospital Universitario de la Princesa (Madrid))
Heras, Inmaculada (Hospital General Universitario Morales Meseguer (Múrcia))
Buño, Ismael (Hospital General Universitario Gregorio Marañón)
Santos, Nazly (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Lloveras, Natàlia (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Velarde, Pilar (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Tuset, Esperanza (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Martínez, Carmen (Hospital Clínic i Provincial de Barcelona)
González, Marcos (Hospital Clínico Universitario (Salamanca))
Sanz, Guillermo F. (Hospital Universitari i Politècnic La Fe (València))
Ferrá, Christelle (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Sampol, Antonia (Hospital Universitari Son Espases (Palma de Mallorca, Balears))
Coll, Rosa (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Pérez-Simón, Jose A. (Universidad de Sevilla)
López-Jiménez, Javier (Hospital Universitario Ramón y Cajal (Madrid))
Jurado, Manuel (Hospital Universitario Virgen de las Nieves (Granada))
Gallardo, David (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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. 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. 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. 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.
Grants:	Instituto de Salud Carlos III PI17/00815 Instituto de Salud Carlos III PI20/01353
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	LAG3: lymphocyte activation gene 3 ; Graft-versus-host disease ; Allogeneic transplant ; Immune response ; Checkpoint molecules
Published in:	Frontiers in immunology, Vol. 14 (january 2023) , ISSN 1664-3224

DOI: 10.3389/fimmu.2023.1066393
PMID: 36742309

9 p, 1.0 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
Articles > Published articles