Morishima Satoko
Division of Endocrinology, Diabetes and Metabolism, Hematology, Rheumatology (Second Department of Internal Medicine), Graduate School of Medicine, University of the Ryukyus.
Rinsho Ketsueki. 2019;60(9):1324-1330. doi: 10.11406/rinketsu.60.1324.
Graft-versus-host disease (GVHD) is a major barrier to successful allogeneic stem cell transplantation. Therefore, the identification of an alternative donor with a lower risk of GVHD is important for patients lacking an HLA-identical sibling donor. To date, HLA studies of large cohorts of unrelated hematopoietic stem cell transplantation (UR-HSCT) have provided important and helpful information for donor selection. In UR-HSCT through Japan Marrow Donor Program, patient and donor HLA-A, -B, and -C, and HLA-DRB1 and -DQB1 double mismatches are significant risk factors for severe GVHD and mortality. HLA-DPB1 mismatch does not affect survival; however, it reduces the chances of leukemia relapse. In the analysis of a specific allele effect on transplant outcomes, HLA-C14:02 was significantly associated with an increased risk of severe acute GVHD. The development of next-generation sequencing (NGS) has enabled full-length HLA allele typing. Evolutionary analysis of the entire HLA-DPB1 revealed that a highly conserved region from exon 3 to 3'UTR provoked acute GVHD that was different from a T-cell epitope mismatching algorithm, reflecting exon 2 polymorphisms. Furthermore, a recent study demonstrated the importance of full-length NGS HLA typing on UR-HSCT outcomes. The usage of NGS may provide important information on the implications of the HLA genes in allogeneic stem cell transplantation.
移植物抗宿主病（GVHD）是异基因干细胞移植成功的主要障碍。因此，对于缺乏 HLA 匹配同胞供者的患者而言，识别具有较低 GVHD 风险的替代供者至关重要。迄今为止，对大量无关造血干细胞移植（UR-HSCT）队列的 HLA 研究为供者选择提供了重要且有用的信息。在通过日本骨髓供者计划进行的 UR-HSCT 中，患者与供者的 HLA-A、-B 和 -C，以及 HLA-DRB1 和 -DQB1 双重错配是严重 GVHD 和死亡的显著危险因素。HLA-DPB1 错配不影响生存；然而，它会降低白血病复发的几率。在分析特定等位基因对移植结果的影响时，HLA-C14:02 与严重急性 GVHD 风险增加显著相关。下一代测序（NGS）技术的发展使得全长 HLA 等位基因分型成为可能。对整个 HLA-DPB1 的进化分析表明，从外显子 3 到 3'UTR 的高度保守区域引发的急性 GVHD 与 T 细胞表位错配算法不同，反映了外显子 2 的多态性。此外，最近一项研究证明了全长 NGS HLA 分型对 UR-HSCT 结果的重要性。NGS 的应用可能为 HLA 基因在异基因干细胞移植中的意义提供重要信息。
