Pathogenesis of experimental lupus nephritis: a role foranti-basement membrane and anti-tubular brush border antibodiesin murine chronic graft-versus-host disease

Abstract

SUMMARY The pathogenesis of renal involvement was studied in murine chronic graft-versus-host disease(GVHD), which is a model for human systemic lupus erythematosus. GVHD was induced by Tour i.v.injections of lymphocytes from DBA/2 donor mice into (C57BL/10 x DBA/2)Fi hybrids at 3-4-dayintervals. Two weeks after the first injection, antibodies were found to have been deposited in themesangium and along the glomerular basement membrane (GBM) in a linear arrangement, whichchanged to a granular pattern after 6–8 weeks. In this stage, large electron-dense complexes werepresent both subepithelially and subendothelially along the GBM. Proteinuria increased up to11 300 ± 2140 μg/ 18 h. Indirect immunofluorescence studies and ELISA showed that sera and kidneyeluates contained autoanlibodies directed against nuclear antigens and GBM component laminin aswell as against renal tubular epithelial antigens (RTE). The specificity of the anti-RTE antibodies wasfurther characterized by the use of absorption techniques as well as immunoblotting. The early linearimmunofluorescence pattern seems to be associated with glomerular binding of anti-GBMantibodies, while electron-dense complex formation in later stages may be induced by thesuperimposed deposition of anti-RTE antibodies. Similar phenomena were recently described inHeymann's nephritis in the rat, a model for human membranous nephropathy.