Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT
Missing KIR ligands are associated with less relapse and increased graft-versus-host disease (GVHD) following unrelated donor allogeneic HCT
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DOI：
10.1182/blood-2007-01-065383
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发表时间：
2007-06-01
期刊：
影响因子：
20.3
通讯作者：
Weisdorf, Daniel J.
中科院分区：
文献类型：
--
作者：
Miller, Jeffery S.;Cooley, Sarah;Weisdorf, Daniel J.
如果供体同种异体反应针对受体，自然杀伤 (NK) 细胞可以改变造血细胞移植 (HCT) 的结果。由于大多数 NK 细胞表达抑制性杀伤免疫球蛋白受体 (KIR)，因此我们假设受体细胞对供体 NK 细胞介导的裂解的敏感性是由缺乏已知 KIR 配体而在遗传上预先确定的。我们分析了 2062 名因急性髓系白血病 (AML；n = 556)、慢性髓系白血病 (CML；n = 1224) 和骨髓增生异常综合征 (MDS；n = 282) 接受无关供体 HCT 的患者的数据。缺失 1 个或多个 KIR 配体与所有配体的存在相比，可防止早期髓系白血病患者复发（相对风险 [RR] = 0.54；n = 536，95% 置信区间 [CI] 0.30-0.95，P =.03）。在接受反式治疗的 CML 患者亚组中（n = 479），缺失 KIR 配体独立预测发生 3-4 级急性移植物抗宿主病的更大风险（GVHD；RR = 1.58，95% CI 1.13-2.22；P =.008）。这些数据支持 NK 细胞在髓系白血病中进行无关 HCT 后的遗传决定作用。
Natural killer (NK) cells can alter the outcome of hematopoietic cell transplantation (HCT) if donor alloreactivity targets the recipient. Since most NK cells express inhibitory killer-immunoglobulin receptors (KIRs), we hypothesized that the susceptibility of recipient cells to donor NK cell-mediated lysis is genetically predetermined by the absence of known KIR ligands. We analyzed data from 2062 patients undergoing unrelated donor HCT for acute myeloid leukemia (AML; n = 556), chronic myeloid leukemia (CML; n = 1224), and myelodysplastic syndrome (MDS; n = 282). Missing 1 or more KIR ligands versus the presence of all ligands protected against relapse in patients with early myeloid leukemia (relative risk [RR] = 0.54; n = 536, 95% confidence interval [CI] 0.30-0.95, P =.03). In the subset of CML patients that received a trans- (n = 479), missing a KIR ligand independently predicted a greater risk of developing grade 3-4 acute graft-versus-host disease (GVHD; RR = 1.58,95% CI 1.13-2.22; P =.008). These data support a genetically determined role for NK cells following unrelated HCT in myeloid leukemia.