不完全相合造血干细胞移植中GVHD的预测研究:模拟HLA抗原结构的比较与应用

采用通用的微量淋巴细胞毒实验和序列测定方法对拟进行造血干细胞移植的患者及供体进行HLA分型；用计算机分子模拟手段，从HLA分子三维结构方面探讨预测移植物抗宿主病（GVHD）发生程度，以预测移植后GVHD的发生情况。结果发现，8例供受体中，3例为半匹配移植，其中2例发生了Ⅳ度GVHD，1例发生了Ⅱ度GVHD；3例为两个抗原不相合移植，其中1例发生了Ⅱ度GVHD，2例发生了Ⅱ度GVHD；2例口才为一个抗原不相合移植，分别发生了Ⅰ度、Ⅱ度GVHD；GVHD的发生程度与HLA不相合抗原RMSD差异的大小呈正相关。提示异基因造血干细胞移植时，GVHD发生程度与HLA分子三维结构的差异有密切关系，三维结构分子模拟进行GVHD预测可以为临床医生提供较好的预后指标。

THE APPLICATION OF MOLECULAR MODELING OF HLA ANTIGENS IN UNMATCHED STEM CELL TRANSPLANTATION FOR GVHD PREDICTION

To explore the pathogenic mechanism of GVHD, attempting to forecast the degree of GVHD after stem cell transplantation, and to enhance the therapeutic effectiveness of clinical transplantation. The conventional microlymphocytotoxicity and sequencing methods were used in typing the HLA. The degrees of GVHD were estimated by molecular modeling of HLA antigens and veryfied the estimation by comparing the clinical results with anticipated degrees. In 8 recipients, three were transplanted with half matched stem cells. Among these 3 pationts, two developed IV degree GVHD, and one developed II degree GVHD. In the other 3 patients, cells of two unmatched HLA antigens were transplanted, and among them one developed I degree GVHD, and two developed II degree GVHD. In two patients who were transplanted with cells of one unmatched HLA antigens, I and II degrees GVHD developed respectively. Second, the correlationship analysis showed that degrees of GVHD had positive correlation with the RMSD (relative mean square deviation) between different HLA antigens. These results indicated that the degrees of GVHD after stem cell transplantation were related with the difference of three dimensional structures of unmatched stem cell HLA antigens; molecular modeling might be used to predict the prognosis of clinical stem cell transplantation.