Effect of MHC and non-MHC donor/recipient genetic disparity on the outcome of allogeneic HCT.

Publication Type:

Journal Article

Source:

Blood, Volume 120, Issue 14, p.2796-2806 (2012)

Keywords:

2012, August 2012, Center-Authored Paper, Clinical Research Division, Genomics Core Facility, Public Health Sciences Division, Vaccine and Infectious Disease Division

Abstract:

The outcome of allogeneic hematopoietic cell transplantation (HCT) is influenced by donor/recipient genetic disparity at loci both inside and outside the Major Histocompatibility Complex (MHC) on chromosome 6p. Although disparity at loci within the MHC is the most important risk factor for the development of severe graft-versus-host disease (GVHD), disparity at loci outside the MHC that encode minor histocompatibility (H) antigens can elicit GVHD and graft-versus-leukemia activity in donor/recipient pairs who are otherwise genetically identical across the MHC. Minor H antigens are created by sequence and structural variation within the genome. The enormous variation that characterizes the human genome suggests that the total number of minor H loci is likely to be large, and ensures that all donor/recipient pairs, despite selection for identity at the MHC, will be mismatched for many minor H antigens. In addition to mismatch at minor H loci, unrelated donor/recipient pairs exhibit genetic disparity at numerous loci within the MHC - particularly HLA-DP - despite selection for identity at HLA-A, -B, -C, and -DRB1. Disparity at HLA-DP exists in 80% of unrelated pairs and clearly influences the outcome of unrelated HCT; the magnitude of this effect likely exceeds that associated with disparity at any locus outside the MHC.