Sasazuki T, Juji T, Morishima Y, Kinukawa N, Kashiwabara H, Inoko H, Yoshida T, Kimura A, Akaza T, Kamikawaji N, Kodera Y, Takaku F
Department of Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
N Engl J Med. 1998 Oct 22;339(17):1177-85. doi: 10.1056/NEJM199810223391701.
The requirements with respect to HLA compatibility and the relative importance of matching for individual class I and class II HLA alleles in the transplantation of hematopoietic stem cells from unrelated donors have not yet been established.
We performed retrospective DNA typing of alleles at 11 polymorphic loci of HLA genes in 440 recipients of hematopoietic stem cells from unrelated donors who were serologically identical with their respective recipients for HLA-A, B, and DR antigens. Of these recipients, 80 percent had leukemia; the rest had lymphoma, marrow failure, or a congenital disorder.
Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001). Mismatching of HLA-A, but not of HLA-C, alleles was an independent risk factor for death (P<0.001). Matching [corrected] of HLA-C alleles was a significant risk factor for relapse of leukemia (P=0.035). HLA-B disparity was a significant risk factor for both GVHD and death in the univariate analysis, but not in multivariate analysis. Disparities in class II HLA alleles of the DRB1, DQA1, DQB1, DPA1, and DPB1 loci were not identified as significant risk factors for acute GVHD or death in the multivariate analysis.
Genomic typing of class I HLA alleles adds substantially to the success of transplantation of hematopoietic stem cells from unrelated donors, even if the donors are serologically identical to their recipients with respect to HLA-A, B, and DR antigens.
关于人类白细胞抗原（HLA）相容性的要求以及在无关供者造血干细胞移植中单个I类和II类HLA等位基因匹配的相对重要性尚未确定。
我们对440例接受无关供者造血干细胞移植的受者进行了HLA基因11个多态性位点等位基因的回顾性DNA分型，这些供者与各自的受者在HLA - A、B和DR抗原的血清学检测上是相同的。在这些受者中，80%患有白血病；其余的患有淋巴瘤、骨髓衰竭或先天性疾病。
多变量分析显示，HLA - A等位基因不相容和HLA - C等位基因不相容是严重急性移植物抗宿主病（GVHD）的独立危险因素（HLA - A，P = 0.006；HLA - C，P = 0.001）。HLA - A等位基因不匹配而非HLA - C等位基因不匹配是死亡的独立危险因素（P < 0.001）。HLA - C等位基因匹配[校正后]是白血病复发的重要危险因素（P = 0.035）。在单变量分析中，HLA - B差异是GVHD和死亡的重要危险因素，但在多变量分析中并非如此。在多变量分析中，DRB1、DQA1、DQB1、DPA1和DPB1位点的II类HLA等位基因差异未被确定为急性GVHD或死亡的重要危险因素。
I类HLA等位基因的基因组分型极大地提高了无关供者造血干细胞移植的成功率，即使供者在HLA - A、B和DR抗原方面与受者血清学检测相同。
