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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
Author(s) -
Ruth D. Allen,
J A Dobkins,
Jill M. Harper,
Denise L. Slayback
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00626.x
Subject(s) - major histocompatibility complex , biology , locus (genetics) , minor histocompatibility antigen , histocompatibility , graft versus host disease , disease , transplantation , immune system , immunology , gene , genetics , chromosome , phenotype , chimera (genetics) , human leukocyte antigen , antigen , stem cell , pathology , medicine , surgery
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 disparity between host and donor for minor histocompatibility antigens. However, it is also possible that other forms of polymorphism, such as polymorphisms in immune effector molecules, might play a significant role in determining GVHD 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 on Chromosome 1 of the mouse, and possibly also a locus on Chromosome 4, exert 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 GVHD‐associated pathology and that gene mapping can be used as a tool to identify these loci. Further analysis of such loci will allow identification of the mechanism whereby they influence GVHD and may lead in the future to improved selection of donors for human bone marrow transplantation.