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 transplantation that can occur in either acute or chronic forms. Much of the long-term pathology seen in chronic GVHD is a result of autoantibody production. In the DBA/2-->B6D2F1 murine model of chronic GVHD, anti-ssDNA autoantibodies 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 donors, which develop acute rather than chronic GVHD. Therefore, in this model, donor genetic factors predispose to the development of chronic GVHD in recipients. We performed a genetic analysis aimed at mapping donor loci that influence the magnitude of early autoantibody production in B6D2F1 recipients of cells from DBA/2 donor mice. Linkage analysis suggested an influence of two loci: a locus on chromosome 11 linked to D11Mit278 and a locus on chromosome 4 linked to D4Mit226. The locus on chromosome 11 also appeared to influence the development of renal pathology associated with chronic GVHD.
Slayback
D L
DL
Department of Biology, IUPUI, Indianapolis, IN 46202, USA.
Dobkins
J A
JA
Harper
J M
JM
Allen
R D
RD
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D002874:Chromosome Mapping; D002908:Chronic Disease; D003433:Crosses, Genetic; D004277:DNA, Single-Stranded / Q000276:immunology*; D008040:Genetic Linkage; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007668:Kidney / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics*; D008811:Mice, Inbred DBA / Q000235:genetics*; D019463:Mice, Inbred MRL lpr; D016133:Polymerase Chain Reaction
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D004277:DNA, Single-Stranded; D005819:Genetic Markers