57-OR

Abstract

Aim Studies demonstrating MHC haplotype matching by linkage between HLA-A, -B and -DRB1 in unrelated Haematopoietic Cell Transplantation (HCT), have demonstrated to reduce acute GVHD but increase the risk of disease recurrence. Thus, knowing the haplotype matching status of HCT donors and recipients may influence the selection of unrelated donors. Currently, there are no efficient ways of determining the degree of MHC haplotype matching, other than inference based on HLA-A, B, C, DRB1 and DQB1. This approach may be unreliable because of the haplotype promiscuity of some of the HLA alleles and the large physical distance between HLA-B/C and HLA-DRB1/DQB1. The aim of this study was to identify new markers to assist with haplotype matching between HCT donors and patients. Methods We sequenced the region within the MHC haplotype block that includes the complement genes (the Gamma block) in homozygous workshop DNA and identified candidate SNP’s using Assign-ATF sequence analysis software. PCR-SSP’s were then developed to type specifically for the candidate SNP’s which were then used for typing on MHC typed sample donors. Results Testing on homozygous DNA and MHC typed sample donors identified SNP’s exclusively specific for 17 common MHC Extended, or Ancestral, Haplotypes and a further 15 SNP’s shared between a small number of haplotypes. Furthermore, testing on HLA identical sample donors has revealed Gamma block mismatching does occur, indicating a high likelihood that the genomic content of a significant portion of the MHC is likely to be mismatched between the donors of these samples. Conclusions We have developed SSP assays, called Gamma-Type™, for MHC haplotype block specific SNPs, located in a critical region of the MHC between HLA-B/C and HLA-DRB1/DQB1. Gamma-Type™ is an important tool for assessing the likelihood of haplotype matching between HCT donors and recipients.