【摘要】 如何准确预测GVHD的发生始终是造血干细胞移植领域中十分棘手的难题。采用HLA抗原三维结构的模型来预测GVHD的发生是移植免疫研究的最新进展之一。我们在对17个移植家系进行筛选时,发现了一个供、受体HLA-A位点不合的家系,临床移植后该患者发生了Ⅳ级GVHD。本实验采用高分辨巢式PCR-SSP和DNA序列测定证实患者的HLA-A位点发生了重组(A~*6901→A~*0201)。进行蛋白质三维结构模型分析显示,供、受体差异抗原的空间构象存在明显差异。可能会成为移植后发生GVHD的分子基础,从而验证了我们的实验结果和理论推断。由此可见,该HLA抗原三维结构模型在预测GVHD的发生中具有重要意义。更多还原

【Abstract】 How to accurately predict GVHD is always a difficult problem in the field of hematopoietic stem cell transplantation. Three-dimensional structure modeling of HLA-A antigens for predicting GVHD occurrence is one of the important progress in the field of transplant immunology. Seventeen families were screened and only one donor-recipient pair with one incompatible antigen in HLA-A locus was found. Acute GVHD (grade Ⅳ) occurred after bone marrow transplantation. The high-resolution nested PCR-SSP methods was applied to further analyze the incompatible HLA-A allelic subtypes and indicated that HLA-A locus of the patient was gene recombination (A* 6901→A* 0201). DNA sequencing results indicated that there were 6 amino acid differences between A* 6901 and A* 0201. Obvious differences between the two HLA antigens were found in their protein conformation models, which might be the molecular basis initiating acute GVHD after transplantation. Three-dimensional structure modeling of HLA-A antigens for predicting GVHD occurrence has significant importance in forecasting GVHD after incompatible HLA donor-recipient hematopoietic stem cell transplantation.更多还原