The Research About Prediction Of Acute GVHD After Allogeneic Umbilical Cord Blood Transplantation

To establish a valid method of predicting acute GVHD (aGVHD) after allogeneic umbilical cord blood transplantation, this study explored the influences of several factors on aGVHD. First, made HLA three-dimensional structure matching by molecular modeling in 26 recipient-donor pairs, and found that serious aGVHD could be predicted accurately through general RMSD which indicate structural differences between donor and recipient. Second, based on HLA high resolution typing in 25 recipient-donor pairs, we found that the proportion of recipient who develop serious aGVHD increased when 3 or more HLA loci were mismatched, and HLA-DRB1 matching had greater influence on aGVHD than HLA class I loci did. Then, we tested KIR genes and analyzed KIR ligands matching in 47 recipient-donor pairs, the results indicated KIRKIR3DS1 and 2DS2 genes carried in donor and absent in recipients could favor engraftment, and the donor's KJR2DS2 gene which absent in recipient preserved recipient against aGVHD; No or slighter aGVHD was observed when recipient's KIR ligands was included in donor's, and serious aGVHD was observed when donor's KIR ligands was included in recipient's. Lastly, by analysis on transplant cases it was found that combined analysis on multi-factor could improve accuracy of predication of aGVHD. Through above researches we got the conclusion: The factors which can induce serious aGVHD are as follow: 1) general RMSD of recipient-donor pair is over 0.5. 2) 3 or more HLA loci are mismatched based on high resolution typing. 3) HLA-DRB1 mismatches. 4) Donor's KIR ligands are included in recipient's. The risk of aGVHD occurrence is very high when transplant cases have 2 ormore kinds of these four factors. The method of comprehensive analysis of above factors can used as a new reliable approach to predict the risk of aGVHD occurrence. This study break through the limitation of simple means of predicting aGVHD solely by HLA matching, established a reliable method to predict aGVHD after allogeneic umbilical cord blood transplantation, and provided basis for donor selection and determination of aGVHD prophylaxis.