The genotype of RAET1L (ULBP6), a ligand for human NKG2D (KLRK1), markedly influences the clinical outcome of allogeneic stem cell transplantation
The genotype of RAET1L (ULBP6), a ligand for human NKG2D (KLRK1), markedly influences the clinical outcome of allogeneic stem cell transplantation
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DOI：
10.1111/bjh.12072
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发表时间：
2012-12-01
影响因子：
6.5
通讯作者：
Moss, Paul
中科院分区：
文献类型：
--
作者：
Antoun, Ayman;Vekaria, Dhruti;Moss, Paul
NKG 2D（KLRK 1）是自然杀伤（NK）细胞和T细胞上的活化受体，并结合由MIC和RAET 1基因家族编码的多种多态性配体。我们研究了异基因干细胞移植（SCT）中视黄酸早期转录本-1（RAET 1）多态性的临床意义，通过测定371例患者-供体对中18个单核苷酸多态性（SNP）和单个RAET 1等位基因的频率，并将其与临床结局相关联。在患者RAET 1 L（ULBP 6）基因中存在5个SNP与无复发生存期和总生存期之间观察到了强相关性。两种常见的RAET 1 L等位基因被确定，患者中保护性RAET 1 L *02等位基因的存在与8年无复发生存率44%相关，而缺乏RAET 1 L *02等位基因的患者仅为25%（P < 0.001）。携带RAET 1 L *02等位基因的患者的总生存率为55%，而缺乏RAET 1 L *02等位基因的患者为39%（P = 0.003）。这些新的发现表明NKG 2DRAET 1 L相互作用在决定SCT临床结果中的关键作用，并表明RAET 1 L可能对调节同种异体反应性免疫应答的强度具有重要影响。这些数据对于指导未来移植治疗方案的制定具有价值。
NKG2D (KLRK1) is an activating receptor on natural killer (NK) and T-cells and binds a diverse panel of polymorphic ligands encoded by the MIC and RAET1 gene families. We studied the clinical importance of retinoic acid early transcript-1 (RAET1) polymorphism in allogeneic stem cell transplantation (SCT) by determining the frequency of 18 single nucleotide polymorphisms (SNPs) and individual RAET1 alleles in 371 patient-donor pairs and relating this to clinical outcome. A strong association was observed between the presence of five SNPs within the patient RAET1L (ULBP6) gene and relapse-free survival and overall survival. Two common alleles of RAET1L were determined and the presence of the protective RAET1L*02 allele in the patient was associated with a relapse-free survival of 44% at 8 years compared with just 25% in patients who lacked a RAET1L*02 allele (P < 0.001). Overall survival at this time was 55% in those with RAET1L*02 allele compared to 39% in patients who lacked a RAET1L*02 allele (P = 0.003). These novel findings indicate a critical role for NKG2DRAET1L interactions in determining SCT clinical outcome and show RAET1L may have an important influence on regulating the strength of the alloreactive immune response. The data will be of value in guiding the development of future transplant therapy protocols.