Bogunia-Kubik Katarzyna
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Arch Immunol Ther Exp (Warsz). 2004 Jul-Aug;52(4):240-9.
Hematopoietic stem cell transplantation (HSCT) is a curative treatment of many hematological disorders. Recent studies have shown the associations between polymorphic features of cytokine-encoding genes and the incidence of post-transplant complications in the recipients of allogeneic HSCT. This review focuses on the relationship between the polymorphic patterns of patient genes encoding tumor necrosis factor (TNF)-alpha and TNF-beta and the manifestation of post-transplant complications, acute graft-versus-host disease (aGvHD), generation of toxic lesions, and mortality. Discussed in more detail are the relationships of TNFd microsatellites and polymorphisms within the promoter region of the TNF-alpha-encoding gene (TNFA in the position (-308) and within the first intron of the TNF-beta-encoding gene (TNFB). It appeared that heterozygosity within the TNFA promoter and the first intron of the (TNFB). It gene increased the susceptibility to severe grades III-IV of toxic complications, while the presence of the TNFd3 homozygous genotype was associated with a higher risk of severe aGvHD and early mortality in patients after allogeneic HSCT. These results imply that donor-recipient genotyping, extended to cytokine loci, may be of prognostic value for transplantation outcome.
造血干细胞移植(HSCT)是治疗多种血液系统疾病的一种根治性方法。最近的研究表明,细胞因子编码基因的多态性特征与异基因造血干细胞移植受者移植后并发症的发生率之间存在关联。本综述重点关注编码肿瘤坏死因子(TNF)-α和TNF-β的患者基因多态性模式与移植后并发症的表现、急性移植物抗宿主病(aGvHD)、毒性损伤的发生以及死亡率之间的关系。更详细地讨论了TNFd微卫星以及编码TNF-α的基因(位于-308位置的TNFA)启动子区域内和编码TNF-β的基因(TNFB)第一个内含子内的多态性。结果显示,TNFA启动子和(TNFB)基因第一个内含子内的杂合性增加了发生III-IV级严重毒性并发症的易感性,而TNFd3纯合基因型的存在与异基因造血干细胞移植后患者发生严重aGvHD和早期死亡的较高风险相关。这些结果表明,扩展到细胞因子基因座的供体-受体基因分型可能对移植结果具有预后价值。