检测肿瘤坏死因子d基因型预测急性重症移植物抗宿主病

The impact of donor TNF-d genotype in the severity of acute GVHD

目的 探讨肿瘤坏死因子d（TNF-d）基因型在急性移植物抗宿主病（aGVHD）发病过程中的意义。方法 选择1997至2000年间进行同胞间骨髓移植的受者51例，根据受者移植后发生aGVHD的程度分为2组。观察组：为Ⅲ／Ⅳ度aGVHD20例，对照组：为0／Ⅰ度aGVHD31例。获取受者及其同胞供者的DNA，通过变性高效液相色谱（DHPLC）法结合DNA测序检测TNF-d基因型。结果 观察组供者的TNF-d3／d3基因型（6／20）检出频率明显高于对照组（2／31）；观察组供者的TNF-d3基因频率（50％）明显高于对照组（27．4％）；两组比较，差异均有统计学意义（P〈0．05）。观察组受者的TNF-d3基因频率（45％）明显高于对照组（17．7％），两组比较，差异均有统计学意义（P〈0．01）。结论 在同胞间的骨髓移植中，供者的TNF-d3／d3基因型以及供、受者的TNF-d3基因频率与Ⅲ／Ⅳ度aGVHD的发生密切相关，检测TNF-d基因型可以预测受者是否发生aGVHD。

Objective To study the impact of tumor necrosis factor d （TNF-d） genotype in the occurrence of acute graft versus host disease （GVHD）. Methods Twenty cases of grade Ⅲ/Ⅳ aGVHD and thirty-one cases of grade 0/Ⅰ aGVHD as controls were included in this study, while no other risk factors were found. TNF-d genotype was analyzed by DHPLC（denature high performance liquid chromatography） and DNA sequencing. Results TNF-d3/d3 genotype was significantly more frequent in the sibling donor of grade Ⅲ/Ⅳ aGVHD patients than in those of grade 0/Ⅰ aGVHD patients（6/20 vs 2/31,P〈0. 05）. TNF-d3 genotype was significantly more frequent in the sibling donor of grade Ⅲ/Ⅳ aGVHD patients than in those of grade 0/Ⅰ degree aGVHD patients （50 % vs 27.4%, P〈0. 05）. Likewise, frequency of TNF-d3 genotype was remarkally more frequent in the patients with grade Ⅲ/Ⅳ aGVHD than in those with grade 0/Ⅰ aGVHD （45 % vs 17. 7 % ,P〈0. 01）. Conclusion TNF-d3/d3 genotype for sibling donor and TNF-d3 genotype for patients and their donors are more frequently associated with severe aGVHD.