H. Lee Moffitt Cancer Center, Tampa, FL;
Blood. 2013 Nov 21;122(22):3651-8. doi: 10.1182/blood-2013-05-501510. Epub 2013 Aug 27.
HLA disparity has a negative impact on the outcomes of hematopoietic cell transplantation (HCT). We studied the independent impact of amino acid substitution (AAS) at peptide-binding positions 9, 99, 116, and 156, and killer immunoglobulin-like receptor binding position 77 of HLA-A, B, or C, on the risks for grade 3-4 acute graft-versus-host disease (GVHD), chronic GVHD, treatment-related mortality (TRM), relapse, and overall survival. In multivariate analysis, a mismatch at HLA-C position 116 was associated with increased risk for severe acute GVHD (hazard ratio [HR] = 1.45, 95% confidence interval [CI] = 1.15-1.82, P = .0016). Mismatch at HLA-C position 99 was associated with increased transplant-related mortality (HR = 1.37, 95% CI = 1.1-1.69, P = .0038). Mismatch at HLA-B position 9 was associated with increased chronic GVHD (HR = 2.28, 95% CI = 1.36-3.82, P = .0018). No AAS were significantly associated with outcome at HLA-A. Specific AAS pair combinations with a frequency >30 were tested for association with HCT outcomes. Cysteine to tyrosine substitution at position 99 of HLA-C was associated with increased TRM (HR = 1.78, 95% = CI 1.27-2.51, P = .0009). These results demonstrate that donor-recipient mismatch for certain peptide-binding residues of the HLA class I molecule is associated with increased risk for acute and chronic GVHD and death.
HLA 错配对造血细胞移植 (HCT) 的结果有负面影响。我们研究了氨基酸取代 (AAS) 在肽结合位 9、99、116 和 156 以及杀伤免疫球蛋白样受体结合位 77 对 HLA-A、B 或 C 的独立影响，这些影响与 3-4 级急性移植物抗宿主病 (GVHD)、慢性 GVHD、治疗相关死亡率 (TRM)、复发和总生存的风险有关。在多变量分析中，HLA-C 位置 116 的不匹配与严重急性 GVHD 的风险增加相关（危险比 [HR] = 1.45，95%置信区间 [CI] = 1.15-1.82，P =.0016）。HLA-C 位置 99 的不匹配与移植相关死亡率增加相关（HR = 1.37，95%CI = 1.1-1.69，P =.0038）。HLA-B 位置 9 的不匹配与慢性 GVHD 增加相关（HR = 2.28，95%CI = 1.36-3.82，P =.0018）。在 HLA-A 中，没有 AAS 与结果显著相关。对频率>30%的特定 AAS 对组合进行了检测，以确定它们与 HCT 结果的关联。HLA-C 位置 99 的半胱氨酸到酪氨酸取代与 TRM 增加相关（HR = 1.78，95%CI = 1.27-2.51，P =.0009）。这些结果表明，HLA Ⅰ类分子某些肽结合残基的供体-受者不匹配与急性和慢性 GVHD 以及死亡风险增加相关。
