Department of Haematology, Jiangsu Institute of Haematology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
HLA Laboratory of Jiangsu Institute of Haematology, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Clin Exp Immunol. 2021 Sep;205(3):417-428. doi: 10.1111/cei.13631. Epub 2021 Jul 6.
Numerous reports suggest that activating killer immunoglobulin-like receptors (aKIRs) of natural killer (NK) cells, in addition to inhibitory KIRs (iKIRs), play a prognostic role after allogeneic haematopoietic stem cell transplantation (allo-HSCT). We aimed to investigate the association between the dynamic expression of KIRs on NK cells and the outcomes, particularly regarding graft-versus-host disease (GvHD). This study retrospectively enrolled 260 pairs of donors and recipients who had undergone allo-HSCT without in-vitro T cell depletion. The mRNA transcription level of KIRs was determined by quantitative real-time polymerase chain reaction (RT-qPCR). The levels of aKIR transcripts were decreased more than those of iKIRs during the occurrence of GvHD. The transcription levels of KIR2DS2 and KIR2DS4 in the patients developing GvHD, compared with those who were at a tolerance state, showed the most significant decrease in the month at their peak transcription levels (p = 0.03, p = 0.002). Significantly decreased expression of KIR2DS1 (p = 0.02), KIR2DS3 (p = 0.04) and KIR2DS5 (p = 0.04) in the GvHD group was observed when the transcription level reached a maximum. High expression of KIR3DS1 was associated with superior overall survival (OS) (p < 0.001). The expression of KIR2DS4 in the KIR genotype Bx group decreased more during GvHD, particularly at 3M (p = 0.02). These findings suggest that KIR genes are potential post-HSCT biomarkers and dynamic changes in the KIR transcription levels can be detected to better predict the occurrence and evaluate the treatment of GvHD after transplantation.
许多报告表明，除了抑制性杀伤细胞免疫球蛋白样受体（iKIRs）外，激活自然杀伤（NK）细胞上的杀伤细胞免疫球蛋白样受体（aKIRs）在异基因造血干细胞移植（allo-HSCT）后具有预后作用。我们旨在研究 NK 细胞上 KIR 动态表达与结果之间的关系，特别是关于移植物抗宿主病（GvHD）。这项研究回顾性地纳入了 260 对未进行体外 T 细胞耗竭的 allo-HSCT 供者和受者。通过实时定量聚合酶链反应（RT-qPCR）测定 KIR 的 mRNA 转录水平。在发生 GvHD 期间，aKIR 转录本的水平降低超过 iKIRs。与处于耐受状态的患者相比，发生 GvHD 的患者的 KIR2DS2 和 KIR2DS4 转录本水平在其转录本水平达到峰值的月份显示出最显著的降低（p=0.03，p=0.002）。在 GvHD 组中，KIR2DS1（p=0.02）、KIR2DS3（p=0.04）和 KIR2DS5（p=0.04）的表达显著降低，当转录水平达到最大值时。KIR3DS1 高表达与总生存（OS）改善相关（p<0.001）。在 GvHD 期间，KIR 基因型 Bx 组中的 KIR2DS4 表达下降更多，特别是在 3M（p=0.02）。这些发现表明 KIR 基因是潜在的 HSCT 后生物标志物，可以检测 KIR 转录水平的动态变化，以更好地预测移植后 GvHD 的发生并评估其治疗效果。
