Genetics of graft-versus-host disease, I. A locus on Chromosome 1 influences development of acute graft-versus-host disease in a major histocompatibility complex mismatched murine model

Graft-versus-host disease (GVHD) is the major complication occurring after bone marrow transplantation. The severity of GVHD varies widely, with this variation generally being attributed to variation in the degree of disparit y between host and donor for minor histocompatibility antigens. However, it is also possible that other forms of polymorphism, such as polymorphisms i n immune effector molecules, might play a significant role in determining G VHD severity. In order to investigate this hypothesis, we are studying the genetic factors that influence GVHD development in a murine model. We here report the first results of this analysis, which demonstrate that a locus o n Chromosome 1 of the mouse, and possibly also a locus on Chromosome 4, exe rt considerable influence over the development of one aspect of acute GVHD- splenomegaly-in a parent-->F-1 murine model. These results demonstrate that non-MHC genes can exert quite significant effects on the development of GV HD-associated pathology and that gene mapping can be used as a tool to iden tify these loci. Further analysis of such loci will allow identification of the mechanism whereby they influence GVHD and may lead in the future to im proved selection of donors for human bone marrow transplantation.