Genetic factors influencing the development of chronic graft-versus-host disease in a murine model

Graft-versus-host disease (GVHD) is a major complication of bone marrow tra nsplantation that can occur in either acute or chronic forms. Much of the l ong-term pathology seen in chronic GVHD is a result of autoantibody product ion. In the DBA/2-->B6D2F1 murine model of chronic GVHD, anti-ssDNA autoant ibodies can be detected by 14 days post cell transfer. These autoantibodies are not observed in B6D2F1 recipients of cells from C57BL/6 or B10.D2 dono rs, which develop acute rather than chronic GVHD, Therefore, in this model, donor genetic factors predispose to the development of chronic GVHD in rec ipients. We performed a genetic analysis aimed at mapping donor loci that i nfluence the magnitude of early autoantibody production in B6D2F1 recipient s of cells from DBA/2 donor mice. Linkage analysis suggested an influence o f two loci: a locus on chromosome 11 linked to D11Mit278 and a locus on chr omosome 4 linked to D4Mit226, The locus on chromosome 11 also appeared to i nfluence the development of renal pathology associated with chronic GVHD.