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Increased disparity for minor histocompatibility antigens as a potential cause of increased GVHD risk in marrow transplantation from unrelated donors compared with related donors.

Patients transplanted with marrow from an HLA-phenotypically identical unrelated donor have a much higher risk of acute graft-versus-host disease (GVHD) than patients transplanted from an HLA-genotypically identical sibling. Much of this increased risk may be due to disparity for antigens encoded by genes within the MHC. Although the development of molecular genetic methods for HLA-typing may enable better matching between unrelated donor/recipient pairs, the extent to which GVHD risk might be decreased remains uncertain because disparity for minor histocompatibility antigens encoded by genes outside the MHC also causes GVHD. By application of fundamental population genetics, it can be demonstrated that the disparity for minor histocompatibility antigens is substantially greater between unrelated individuals than between family members. These findings imply that even with improved HLA-matching, unrelated marrow transplantation will carry more risk of GVHD than transplantation from a related donor.