Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation
Donor and recipient chemokine receptor CCR5 genotype is associated with survival after bone marrow transplantation
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DOI：
10.1182/blood-2009-08-237768
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发表时间：
2010-03-18
期刊：
影响因子：
20.3
通讯作者：
Abdi, Reza
中科院分区：
文献类型：
--
作者：
McDermott, David H.;Conway, Susan E.;Abdi, Reza
尽管造血干细胞移植（HSCT）的进展不断，但其发病率和死亡率仍然很高。趋化因子在HSCT中的重要性在于它们对决定移植结果的免疫应答的调节。我们采用多变量考克斯回归模型，在1370例广泛人类白细胞抗原匹配、无关的供受者中，采用候选基因方法，研究受体和供者趋化因子系统基因多态性对移植物抗宿主病发病率和移植后结局的作用。我们的分析发现，一个共同的CCR 5单倍型（H1/H1）纯合子受体有更好的无病生存（DFS; P = 0.005）和总生存（P = 0.021）。当模型中考虑供体和受体的相同基因型时，注意到与DFS和总生存率高度显著相关（P < .001和P = .007，移植后3年，两组间的生存率绝对差异高达20（对于具有受体CCR 5 H1/H1的对，DFS为50%，而对于具有供体CCR 5 H1/H1的对，DFS为30%）。这一发现表明供体和/或受体CCR 5基因型可能与HSCT结果相关，并提出了优化治疗的新诊断和治疗策略。（血。2010; 115：2311- 2318）
Despite continual improvement, morbidity and mortality after hematopoietic stem cell transplantation (HSCT) remain high. The importance of chemokines in HSCT lies in their regulation of immune responses that determine transplantation outcomes. We investigated the role of recipient and donor chemokine system gene polymorphisms by using a candidate gene approach on the incidence of graft-versus-host disease and posttransplantation outcomes in 1370 extensively human leukocyte antigen-matched, unrelated donor-recipient pairs by using multivariate Cox regression models. Our analysis identified that recipients homozygous for a common CCR5 haplotype (H1/H1) had better disease-free survival (DFS; P = .005) and overall survival (P = .021). When the same genotype of both the donor and recipient were considered in the models, a highly significant association with DFS and overall survival was noted (P < .001 and P = .007, respectively) with absolute differences in survival of up to 20% seen between the groups at 3 years after transplantation (50% DFS for pairs with recipient CCR5 H1/H1 vs 30% for pairs with donor CCR5 H1/H1). This finding suggests that donor and/or recipient CCR5 genotypes may be associated with HSCT outcome and suggests new diagnostic and therapeutic strategies for optimizing therapy. (Blood. 2010; 115: 2311- 2318)