High HLA-DP Expression and Graft-versus-Host Disease.
High HLA-DP Expression and Graft-versus-Host Disease.
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DOI：
10.1056/nejmoa1500140
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发表时间：
2015-08-13
期刊：
影响因子：
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通讯作者：
Stevenson P
中科院分区：
文献类型：
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作者：
Petersdorf EW;Malkki M;O'hUigin C;Carrington M;Gooley T;Haagenson MD;Horowitz MM;Spellman SR;Wang T;Stevenson P
来自无关供体的造血细胞的移植可以治愈血液疾病，但具有急性移植物抗宿主病（GVHD）的显著风险。当受者和供者HLA-DPB 1不匹配时，风险较高，但导致GVHD的机制尚不清楚。HLA-DPB 1调节区变异体rs 9277534与HLA-DPB 1表达相关。我们检验了GVHD风险与受体中与错配HLA-DPB 1连锁的rs 9277534等位基因相关的假设。我们对3505人进行rs 9277534基因分型，以确定rs 9277534-DPB 1单倍型。在1441例来自HLA-A、B、C、DRB 1、DQB 1匹配的非亲缘供者的移植受者中，确定rs 9277534 A和G等位基因与HLA-DPB 1错配的连锁。通过定量聚合酶链反应测定评估HLA-DPB 1表达。将HLA-DPB 1错配等位基因与rs 9277534 G（高表达）连锁的受者中急性GVHD的风险与HLA-DPB 1错配等位基因与rs 9277534 A（低表达）连锁的受者中急性GVHD的风险进行比较。rs 9277534 A的平均HLA-DPB 1表达低于rs 9277534 G。在来自rs 9277534 A连锁HLA-DPB 1供者的移植受者中，rs 9277534 G连锁HLA-DPB 1错配受者的急性GVHD风险高于rs 9277534 A连锁HLA-DPB 1错配受者（风险比，1.54; 95%可信区间[CI]，1.25 ~ 1.89; P<0.001），因疾病复发以外原因死亡的风险也是如此（风险比，1.25; 95% CI，1.00 - 1.57; P = 0.05）。与HLA-DPB 1错配相关的GVHD风险受HLA-DPB 1 rs 9277534表达标志物的影响。在来自低表达等位基因供体的HLA-DPB 1错配移植的受者中，高表达等位基因的受者具有较高的GVHD风险。（由美国国立卫生研究院和其他机构资助。
Transplantation of hematopoietic cells from unrelated donors can cure blood disorders but carries a significant risk of acute graft-versus-host disease (GVHD). The risk is higher when the recipient and donor are HLA-DPB1–mismatched, but the mechanisms leading to GVHD are unknown. The HLA-DPB1 regulatory region variant rs9277534 is associated with HLA-DPB1 expression. We tested the hypothesis that the GVHD risk correlates with the rs9277534 allele linked to the mismatched HLA-DPB1 in the recipient. We genotyped rs9277534 in 3505 persons to define rs9277534-DPB1 haplotypes. Among 1441 recipients of transplants from HLA-A,B,C,DRB1,DQB1–matched unrelated donors with only one HLA-DPB1 mismatch, linkage of the rs9277534 A and G alleles to the mismatched HLA-DPB1 was determined. HLA-DPB1 expression was assessed by means of a quantitative polymerase-chain-reaction assay. The risk of acute GVHD among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534G (high expression) was compared with the risk among recipients whose mismatched HLA-DPB1 allele was linked to rs9277534A (low expression). The mean HLA-DPB1 expression was lower with rs9277534A than with rs9277534G. Among recipients of transplants from donors with rs9277534A-linked HLA-DPB1, the risk of acute GVHD was higher for recipients with rs9277534G-linked HLA-DPB1 mismatches than for recipients with rs9277534A-linked HLA-DPB1 mismatches (hazard ratio, 1.54; 95% confidence interval [CI], 1.25 to 1.89; P<0.001), as was the risk of death due to causes other than disease recurrence (hazard ratio, 1.25; 95% CI, 1.00 to 1.57; P = 0.05). The risk of GVHD associated with HLA-DPB1 mismatching was influenced by the HLA-DPB1 rs9277534 expression marker. Among recipients of HLA-DPB1–mismatched transplants from donors with the low-expression allele, recipients with the high-expression allele had a high risk of GVHD. (Funded by the National Institutes of Health and others.)