A UGT2B17‐positive donor is a risk factor for higher transplant‐related mortality and lower survival after bone marrow transplantation
A UGT2B17‐positive donor is a risk factor for higher transplant‐related mortality and lower survival after bone marrow transplantation
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DOI：
10.1111/j.1365-2141.2005.05427.x
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发表时间：
2005-04
影响因子：
6.5
通讯作者：
S. Terakura;M. Murata;T. Nishida;N. Emi;Y. Akatsuka;S. Riddell;Y. Morishima;Y. Kodera;T. Naoe
中科院分区：
文献类型：
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作者：
S. Terakura;M. Murata;T. Nishida;N. Emi;Y. Akatsuka;S. Riddell;Y. Morishima;Y. Kodera;T. Naoe
我们最近鉴定了一种人类次要组织相容性 (H) 抗原，由 UDP 糖基转移酶 2 家族多肽 B17 (UGT2B17) 编码，其免疫原性是由于 UGT2B17 基因纯合缺失导致供体和受体细胞中的差异表达所致。 UGT2B17 在肝脏和结肠中高表达，是移植物抗宿主病 (GVHD) 的主要靶点。为了评估纯合 UGT2B17 基因缺失在同种异体造血干细胞移植 (HSCT) 中的重要性，我们使用序列特异性引物聚合酶链反应分析了 435 名患有血液恶性肿瘤的干细胞移植受者及其人类白细胞抗原相同的无关骨髓供体的 DNA。在 85% 的正常供体和 82% 的患者中观察到 UGT2B17 基因纯合缺失。分析显示UGT2B17在GVHD方向上的错配与急性GVHD、慢性GVHD、复发或生存的发生率之间没有显着关联。然而，使用 UGT2B17 阳性供体是移植相关死亡率较高和移植后生存率较低的独立危险因素。 UGT2B17 是一种激素、药物和潜在有毒外源化合物的代谢酶，在造血细胞亚群中表达。因此，供体细胞中UGT2B17的酶功能可能会影响同种异体HSCT的结果。
We recently identified a human minor histocompatibility (H) antigen, encoded by UDP glycosyltransferase 2 family, polypeptide B17 (UGT2B17), whose immunogenicity results from differential expression in donor and recipient cells as a consequence of a homozygous deletion of the UGT2B17 gene. UGT2B17 is highly expressed in the liver and colon, which are major targets for graft‐versus‐host disease (GVHD). To assess the significance of homozygous UGT2B17 gene deletion in allogeneic haematopoietic stem cell transplantation (HSCT), we analysed DNA from 435 stem cell transplant recipients with a haematological malignancy and their human leucocyte antigen‐identical unrelated bone marrow donors using sequence‐specific primer polymerase chain reaction. Homozygous deletion of the UGT2B17 gene was observed in 85% of normal donors and in 82% of patients. The analysis showed no significant association between UGT2B17 mismatch in the GVHD direction and the incidence of acute GVHD, chronic GVHD, relapse, or survival. However, the use of a UGT2B17‐positive donor was an independent risk factor for higher transplant‐related mortality and lower survival after transplantation. UGT2B17 is a metabolic enzyme for hormones, drugs, and potentially toxic exogenous compounds and is expressed in subsets of haematopoietic cells. Thus, the enzyme function of UGT2B17 in donor cells may affect the outcome of allogeneic HSCT.