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

被引:2
|
作者
Cruz, David [1 ]
Rodriguez-Romanos, Rocio [1 ]
Gonzalez-Bartulos, Marta [1 ]
Garcia-Cadenas, Irene [2 ]
de la Camara, Rafael [3 ]
Heras, Inmaculada [4 ]
Buno, Ismael [5 ]
Santos, Nazly [1 ]
Lloveras, Natalia [1 ,6 ]
Velarde, Pilar [1 ]
Tuset, Esperanza [1 ]
Martinez, Carmen [7 ]
Gonzalez, Marcos [8 ]
Sanz, Guillermo F. F. [9 ]
Ferra, Christelle [10 ]
Sampol, Antonia [11 ]
Coll, Rosa [1 ,6 ]
Perez-Simon, Jose A. A. [12 ]
Lopez-Jimenez, Javier [13 ]
Jurado, Manuel [14 ]
Gallardo, David [1 ,6 ]
机构
[1] Hosp Dr Josep Trueta, Josep Carreras Res Inst, Inst Catala Oncol, Inst Invest Biomed Girona IDIBGI,Hematol Dept, Hosp Dr, Girona, Spain
[2] Univ Autonoma Barcelona, Hosp Santa Creu & St Pau, Inst Invest Biomed St Pau, Hematol Dept, Barcelona, Spain
[3] Hosp Princesa, Hematol Dept, Madrid, Spain
[4] Hosp Gen Univ Morales Meseguer, Hematol Dept, Murcia, Spain
[5] Univ Complutense Madrid, Hosp Gen Univ Gregorio Maranon, Gregorio Maranon Hlth Res Inst IiSGM, Hematol Dept, Madrid, Spain
[6] Univ Girona, Dept Med, Girona, Spain
[7] Hosp Clin Barcelona, Inst Invest Biomed August Pi i Sunyer IDIBAPS, Hematol Dept, Barcelona, Spain
[8] Hosp Clin Univ, Hematol Dept, Salamanca, Spain
[9] Hosp Univ & Politecn La Fe, Hematol Dept, Valencia, Spain
[10] Hosp Badalona Germans Trias & Pujol, Josep Carreras Res Inst, Inst Catala Oncol, Hematol Dept, Badalona, Spain
[11] Hosp Univ Son Espases, IdISBa, Hematol Dept, Palma De Mallorca, Spain
[12] Univ Seville, Hosp Univ Virgen Rocio, Inst Biomed Sevilla, Hematol Dept, Seville, Spain
[13] Hosp Univ Ramon & Cajal, Hematol Dept, Madrid, Spain
[14] Hosp Univ Virgen Nieves, Hematol Dept, Granada, Spain
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
关键词
LAG3; lymphocyte activation gene 3; graft-versus-host disease; allogeneic transplant; immune response; checkpoint molecules; SYSTEMIC-LUPUS-ERYTHEMATOSUS; STEM-CELL TRANSPLANTATION; LUNG-CANCER; T-CELLS; SUSCEPTIBILITY; POLYMORPHISM; EXPRESSION; PROTEIN; PD-1;
D O I
10.3389/fimmu.2023.1066393
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
IntroductionThe 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. MethodsTo 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. ResultsWe 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. DiscussionWe 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.
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页数:9
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