Yoshizawa Seiichiro, Kitahara Toshihiko, Zhang Yu, Akahane Daigo, Gotoh Moritaka, Ohyashiki Kazuma, Ohyashiki Michiyo, Ohyashiki Junko H
First Department of Internal Medicine, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Shinjuku-ku, Tokyo, Japan.
Hematology. 2010 Dec;15(6):397-405. doi: 10.1179/102453310X12719010991704.
Donor killer immunoglobulin-like receptor (KIR) and KIR-ligand mismatch is considered vital in clarifying the mechanism of natural killer (NK) cell alloreactivity in hematopoietic stem cell transplantation (HSCT). In practical terms, however, it may be difficult to analyze the KIR genotype of donor cells directly as all donor cells are used for the transplant rather than for research purposes. To accurately estimate donor KIR genotype, we determined recipient KIR genotyping sequentially, at a minimum of two time points, using 19 KIR-specific primers in 10 patients who underwent HSCT. Among 10 patients, four had a KIR-ligand mismatch in the graft versus host direction. Sequential KIR genotyping showed the genotype changes at the time of engraftment (donor-derived) as well as relapse (recipient-derived). Our results highlight the utility of sequential KIR genotyping to better understand ligand-ligand, KIR-KIR, or ligand-KIR mismatches. Further studies, including a functional assay of NK cells may clarify the underlying mechanism of KIR ligand-donor KIR mismatch in HSCT.
供体杀伤细胞免疫球蛋白样受体（KIR）与KIR配体错配被认为对于阐明造血干细胞移植（HSCT）中自然杀伤（NK）细胞同种异体反应性机制至关重要。然而，实际上，由于所有供体细胞都用于移植而非研究目的，直接分析供体细胞的KIR基因型可能很困难。为了准确估计供体KIR基因型，我们在10例接受HSCT的患者中，使用19种KIR特异性引物，至少在两个时间点依次对受体进行KIR基因分型。在10例患者中，有4例在移植物抗宿主方向存在KIR配体错配。连续KIR基因分型显示在植入时（供体来源）以及复发时（受体来源）基因型发生了变化。我们的结果突出了连续KIR基因分型在更好地理解配体-配体、KIR-KIR或配体-KIR错配方面的实用性。包括NK细胞功能测定在内的进一步研究可能会阐明HSCT中KIR配体-供体KIR错配的潜在机制。
