Li Lucy, Kolk Merle, Fernandez-Vina Marcelo, de Lima Marcos, Otegbeye Folashade
Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Stem Cell Transplant Program, University Hospitals Seidman Cancer Center, Cleveland, OH, USA.
Bone Marrow Transplant. 2020 Dec;55(12):2294-2297. doi: 10.1038/s41409-020-0957-7. Epub 2020 May 27.
The effects of donor-derived natural killer (NK) cell alloreactivity on disease relapse and transplant-related mortality following allogeneic stem cell transplantation have been described while the impact of recipient-derived NK cell alloreactivity on donor engraftment is not well known. Epitopes of HLA Class I molecules act as ligands for NK cell killer immunoglobulin-like receptors (KIR) regulating their cytotoxicity. As such, NK cell alloreactivity is predictable from KIR ligand mismatches between donors and recipients. We analyzed the impact of KIR ligand mismatch (KIR-L-MM) on donor engraftment in 70 cord blood transplants (CBT) and 26 haploidentical transplants (HaploSCT). In CBT, host-versus-graft-directed KIR-L-MM predicted primary graft failure; an effect not mitigated by use of ATG. This trend was most significant with HLA-C KIR-L-MM. In addition, graft-versus-host-directed KIR-L-MM predicted the dominant cord blood unit in double CBT. In the limited HaploSCT cohort, host-versus-graft-directed KIR-L-MM did not predict graft failure. Time to neutrophil engraftment was unaffected by KIR-L-MM in either CBT or HaploSCT. The direction of KIR-L mismatch may be a parameter to consider when selecting CBT units to ensure successful engraftment. The role of KIR-L-MM in CBT and HaploSCT engraftment merits further exploration in a large transplant database.
供体来源的自然杀伤（NK）细胞同种异体反应性对异基因干细胞移植后疾病复发和移植相关死亡率的影响已有描述，而受体来源的NK细胞同种异体反应性对供体植入的影响尚不清楚。HLA I类分子的表位作为NK细胞杀伤免疫球蛋白样受体（KIR）的配体，调节其细胞毒性。因此，NK细胞同种异体反应性可通过供体和受体之间的KIR配体错配来预测。我们分析了KIR配体错配（KIR-L-MM）对70例脐血移植（CBT）和26例单倍体移植（HaploSCT）中供体植入的影响。在CBT中，宿主对移植物的KIR-L-MM可预测原发性移植物失败；使用抗胸腺细胞球蛋白（ATG）并不能减轻这种影响。这种趋势在HLA-C KIR-L-MM中最为显著。此外，移植物对宿主的KIR-L-MM可预测双份CBT中的优势脐血单位。在有限的HaploSCT队列中，宿主对移植物的KIR-L-MM不能预测移植物失败。在CBT或HaploSCT中，中性粒细胞植入时间不受KIR-L-MM的影响。在选择CBT单位以确保成功植入时，KIR-L错配的方向可能是一个需要考虑的参数。KIR-L-MM在CBT和HaploSCT植入中的作用值得在大型移植数据库中进一步探索。
