Horio Tomohiro, Mizuno Shohei, Uchino Kaori, Mizutani Motonori, Hanamura Ichiro, Espinoza J Luis, Onizuka Makoto, Kashiwase Koichi, Morishima Yasuo, Fukuda Takahiro, Kodera Yoshihisa, Doki Noriko, Miyamura Koichi, Mori Takehiko, Takami Akiyoshi
Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
Transpl Immunol. 2017 Jun;42:34-39. doi: 10.1016/j.trim.2017.05.003. Epub 2017 May 6.
The chemokine receptor CCR5 plays roles in the trafficking of effector cells towards the site of inflammation. We retrospectively examined the impact of the CCR5 variation (rs1800023, -2086A>G) on transplant outcomes in a cohort of 329 patients who underwent unrelated HLA-matched bone marrow transplantation (BMT) for hematologic malignancies through the Japan Marrow Donor Program. A multivariate analysis showed that the recipient CCR5 -2086A/A genotype was significantly associated with a lower relapse rate but not with the development of graft-versus-host disease (GVHD) or transplant-related mortality, thereby resulting in better disease-free and overall survival rates than other variations. The donor CCR5 -2086A/A genotype was associated with a lower incidence of grades 3-4 acute GVHD, which did not improve the survival outcomes. These findings suggest that the recipient CCR5 -2086A/A genotype affects the induction of the graft-versus-tumor effect without augmenting the development of GVHD. CCR5 genotyping in transplant recipients may therefore be a useful tool for evaluating pretransplantation risks.
趋化因子受体CCR5在效应细胞向炎症部位的转运中发挥作用。我们回顾性研究了CCR5变异(rs1800023,-2086A>G)对329例通过日本骨髓供者计划接受非亲缘HLA匹配骨髓移植(BMT)治疗血液系统恶性肿瘤患者移植结局的影响。多因素分析显示,受者CCR5 -2086A/A基因型与较低的复发率显著相关,但与移植物抗宿主病(GVHD)的发生或移植相关死亡率无关,因此与其他变异相比,无病生存率和总生存率更高。供者CCR5 -2086A/A基因型与3-4级急性GVHD的较低发生率相关,但未改善生存结局。这些发现表明,受者CCR5 -2086A/A基因型在不增加GVHD发生的情况下影响移植物抗肿瘤效应的诱导。因此,对移植受者进行CCR5基因分型可能是评估移植前风险的有用工具。