Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation.
Major-histocompatibility-complex class I alleles and antigens in hematopoietic-cell transplantation.
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DOI：
10.1056/nejmoa011826
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发表时间：
2001-12-20
影响因子：
158.5
通讯作者：
Anasetti, C
中科院分区：
文献类型：
--
作者：
Petersdorf, EW;Hansen, JA;Anasetti, C
背景：来自非血缘关系供者的造血干细胞的成功植入受到供者和受者之间的差异的影响。在血清学上可检测到的HLA序列多态之间的差异被称为抗原不匹配，而那些只能通过基于DNA的分型方法识别的被称为等位基因不匹配。目前尚不清楚这两种基因多态性是否在移植中起重要作用。我们测试了一个假设，即只能在DNA水平上检测到的等位基因错配比那些在血清学上可检测到的等位基因错配的免疫原性更差，因此与造血细胞移植后移植失败的风险较低相关。方法：我们使用DNA测序来确定471名接受非血缘关系捐赠者的骨髓治疗慢性髓系白血病的患者的HLA-A、B和C等位基因。结果：单个HLA等位基因错配并不增加移植失败的风险，而单个抗原错配则显著增加移植失败的风险。如果受者在第I类基因不匹配，或者如果供者有两个或更多第I类错配，风险也会增加。结论：血清学可检测到的第I类抗原错配增加了造血细胞移植后移植物失败的风险。来自单个I类等位基因不匹配且血清学无法检测到的供者的移植可以在不增加移植失败风险的情况下使用。(N Engl J Med 2001；345：1794-800)版权所有(C)2001年马萨诸塞州医学会。
Background: Successful engraftment of hematopoietic stem cells from unrelated donors is influenced by disparities between the donor and recipient for HLA-A, B, and C alleles. Disparities between HLA sequence polymorphisms that are serologically detectable are termed antigen mismatches, whereas those that can be identified only by DNA-based typing methods are termed allele mismatches. Whether both kinds of polymorphisms are important in transplantation is not known. We tested the hypothesis that allele mismatches that are detectable only at the DNA level are less immunogenic than those that are serologically detectable and thereby are associated with a lower risk of graft failure after hematopoietic-cell transplantation.Methods: We used DNA sequencing to define the HLA-A, B, and C alleles in 471 patients who received bone marrow from unrelated donors for the treatment of chronic myeloid leukemia after myeloablative conditioning therapy. The odds ratios for graft failure were determined for recipients of transplants from donors with a single class I allele mismatch, a single class I antigen mismatch, or two or more class I mismatches, as compared with those with no mismatch.Results: A single HLA allele mismatch did not increase the risk of graft failure, whereas a single antigen mismatch significantly increased the risk. The risk was also increased if the recipient was HLA homozygous at the mismatched class I locus or if the donor had two or more class I mismatches.Conclusions: HLA class I antigen mismatches that are serologically detectable confer an enhanced risk of graft failure after hematopoietic-cell transplantation. Transplants from donors with a single class I allele mismatch that is not serologically detectable may be used without an increased risk of graft failure. (N Engl J Med 2001;345:1794-800.) Copyright (C) 2001 Massachusetts Medical Society.