Scientists claim that predicting whether a patient receiving a bone marrow transplant from an unrelated HLA-matched donor will develop graft-versus-host disease (GVHD) may be possible by looking to see whether both individuals carry the same SNPs within the major histocompatibility complex (MHC). A team led by Fred Hutchinson Cancer Research Center scientists has found that if one of a donor-recipient pair carries MHC SNP rs887464, while the other carries SNP rs2281389, then the recipient is more likely to develop GVHD or have poorer disease-free survival.
The team made their discovery by genotyping 1120 SNPs residing within the MHC region in samples from over 2,000 transplant HLA-matched recipient and donor pairs, and confirmed their findings in a validation cohort comprising another 1600 patients. Fortunately, when Effie Petersdorf, M.D., and colleagues analyzed the DNA of potential HLA-matched donors for any one recipient, they discovered it was generally possible to find a donor individual who carried the same MHC SNP as the recipient.
Reporting their discovery in Science Translational Medicine, the authors say screening for the presence of the two SNPs in potential donors and patients may help select the most appropriate donor for any one recipient. The next step will then be to sequence the MHC region of genes close to the SNP locations in order to try and identify which are directly responsible for the association between SNP, GVHD, and survival. “Once we discover those genes we will characterize them and then we may be able to further refine donor matching," Dr. Petersdorf says.
The researchers describe their findings in a paper titled “MHC-Resident Variation Affects Risks After Unrelated Donor Hematopoietic Cell Transplantation.”