Hematology Department, Institut Català d'Oncologia - Hospital Dr. Josep Trueta, Institut d'Investigació Biomèdica de Girona (IDIBGI), Josep Carreras Research Institute, Girona, Spain.
Hematology Department, Hospital de la Santa Creu i Sant Pau, Institut d'Investigació Biomèdica Sant Pau, Universitat Autónoma de Barcelona, Barcelona, Spain.
Front Immunol. 2023 Jan 20;14:1066393. doi: 10.3389/fimmu.2023.1066393. eCollection 2023.
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.
已描述参与免疫反应（检查点抑制剂）的分子中的多态性与同种异体造血干细胞移植（alloHSCT）后的临床结果之间的关联。淋巴细胞激活 3（LAG3）是一种表面蛋白，作为抑制性免疫检查点分子在免疫中发挥调节作用。
为了确定其在 alloHSCT 环境中的作用，我们分析了 797 名从 HLA 完全匹配的同胞供体移植的患者。在供体中对 LAG3 rs870849 C>T 多态性进行了基因分型。
我们发现在从 TT 基因型供体移植的患者中，严重急性移植物抗宿主病的发生率更高（p：0.047，HR 1.64；95%CI 1.01 - 2.67）。从 rs870849 CT/TT 基因型供体移植的患者总生存率（OS）更差（0.020；HR，1.44；95%CI 1.06 - 1.96），无病生存率（DFS）（p：0.002；HR 1.58，95%CI：1.18 - 2.14）和移植相关死亡率（TRM）（p< 0.001；HR：1.88，95%CI 1.29 - 2.74）。当结合供体的 LAG3 rs870849 和 PDCD1 rs36084323 基因型时，可以很好地定义三个遗传组，从而可以很好地分层急性移植物抗宿主病，TRM，OS 和 DFS 的风险。
我们得出结论，供体的 LAG3 基因型可以在供体选择中考虑。由于这种选择在 HLA 完全匹配的同胞供体情况下可能受到限制，因此需要进一步研究探索供体 LAG3 基因型在无关移植中的影响。
