Uchino Kaori, Mizuno Shohei, Sato-Otsubo Aiko, Nannya Yasuhito, Mizutani Motonori, Horio Tomohiro, Hanamura Ichiro, Espinoza J Luis, Onizuka Makoto, Kashiwase Koichi, Morishima Yasuo, Fukuda Takahiro, Kodera Yoshihisa, Doki Noriko, Miyamura Koichi, Mori Takehiko, Ogawa Seishi, Takami Akiyoshi
Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Oncotarget. 2017 Jul 11;8(28):45670-45686. doi: 10.18632/oncotarget.17315.
The Toll-like receptor family mediates the innate immune system through recognizing the molecular patterns of microorganisms and self-components and leading the synthesis of the inflammatory mediators. We retrospectively examined whether or not genetic variations in toll-like receptor 1 (rs5743551, -7202GQ>A), toll-like receptor 2 (rs7656411, 22215G>T), and toll-like receptor 4 (rs11536889, +3725G>C) affected transplant outcomes in a cohort of 365 patients who underwent unrelated HLA-matched bone marrow transplantation (for hematologic malignancies through the Japan Marrow Donor Program. Only donor toll-like receptor 4 variation significantly improved the survival outcomes. A multivariate analysis showed that the donor toll-like receptor 4 +3725G/G genotype was significantly associated with a better 5-year progression-free survival and a lower 5-year transplant-related mortality than other variations. Furthermore, the donor toll-like receptor 4 +3725G/G genotype was associated with a significantly lower incidence of fatal infections than other variations. The validation study of 502 patients confirmed that the donor toll-like receptor 4 +3725G/G genotype was associated with better survival outcomes. Toll-like receptor4 genotyping in transplant donors may therefore be a useful tool for optimizing donor selection and evaluating pretransplantation risks.
Toll样受体家族通过识别微生物和自身成分的分子模式并引导炎症介质的合成来介导先天免疫系统。我们回顾性研究了Toll样受体1（rs5743551，-7202GQ>A）、Toll样受体2（rs7656411，22215G>T）和Toll样受体4（rs11536889，+3725G>C）的基因变异是否影响了365例接受无关HLA匹配骨髓移植患者（通过日本骨髓捐赠计划治疗血液系统恶性肿瘤）的移植结果。只有供体Toll样受体4变异显著改善了生存结果。多变量分析显示，与其他变异相比，供体Toll样受体4 +3725G/G基因型与更好的5年无进展生存率和更低的5年移植相关死亡率显著相关。此外，与其他变异相比，供体Toll样受体4 +3725G/G基因型与致命感染的发生率显著降低相关。对502例患者的验证研究证实，供体Toll样受体4 +3725G/G基因型与更好的生存结果相关。因此，对移植供体进行Toll样受体4基因分型可能是优化供体选择和评估移植前风险的有用工具。
