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.

中文翻译：

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供体来源激活KIR基因的动态mRNA表达及其对造血干细胞移植后临床结果的显着影响

许多报告表明，除了抑制性 KIR (iKIR) 外，激活自然杀伤 (NK) 细胞的杀伤性免疫球蛋白样受体 (aKIR) 在同种异体造血干细胞移植 (allo-HSCT) 后发挥预后作用。我们旨在研究 KIR 在 NK 细胞上的动态表达与结果之间的关联，特别是在移植物抗宿主病 (GvHD) 方面。本研究回顾性招募了 260 对未经体外接受过 allo-HSCT 的供体和受体T细胞耗竭。通过定量实时聚合酶链反应（RT-qPCR）测定 KIR 的 mRNA 转录水平。在 GvHD 发生期间，aKIR 转录物的水平比 iKIR 的水平下降更多。与处于耐受状态的患者相比，发生 GvHD 的患者中 KIR2DS2 和 KIR2DS4 的转录水平在其峰值转录水平的月份显示出最显着的下降（p  = 0.03，p  = 0.002）。KIR2DS1 ( p  = 0.02)、KIR2DS3 ( p  = 0.04) 和 KIR2DS5 ( p = 0.04) 在转录水平达到最大值时观察到 GvHD 组。KIR3DS1 的高表达与优越的总生存期 (OS) 相关 ( p  < 0.001)。在 GvHD 期间，KIR 基因型 Bx 组中 KIR2DS4 的表达下降更多，尤其是在 3M 时（p  = 0.02）。这些发现表明，KIR 基因是潜在的 HSCT 后生物标志物，可以检测到 KIR 转录水平的动态变化，以更好地预测 GvHD 的发生并评估移植后的治疗。