Pathogenesis of trypanosomiasis-induced glomerulonephritis in mice.
We investigated the pathogenesis of glomerulonephritis in mice that had been infected with Trypanosoma brucei. Polyclonal B cell activation was evaluated, with special attention to the presence of autoantibodies, which are known to be involved in other models for glomerulonephritis. The BALB/c mice studied developed severe albuminuria. Light-microscopy of the kidneys showed increase of mesangial matrix and thickening of the glomerular capillary walls. Immunofluorescence studies showed immunoglobulins in a mixed linear-granular pattern along the glomerular capillary wall and in the mesangium. Trypanosomal antigens were not found in these aggregates. Electron-microscopy revealed mesangial, subendothelial, and subepithelial electron-dense deposits. During the course of this infection, significant levels of antibodies directed against known nephritogenic renal autoantigens, i.e. GBM, laminin, RTE, and gp330, were measured in serum and glomerular eluates. These findings led us to conclude that mice infected with T. brucei and treated with diminazene aceturate develop an autoimmune-mediated glomerulonephritis, characterized by mesangial, subendothelial, and subepithelial immune aggregates. This murine model seems to offer a useful tool for the study of immunological aspects of polyclonal B cell activation in infection-related glomerular disease.
van Velthuysen
M L
ML
Department of Pathology, University of Leiden, The Netherlands.
Bruijn
J A
JA
van Leer
E H
EH
Fleuren
G J
GJ
D000818:Animals; D000906:Antibodies / Q000032:analysis; D001485:Basement Membrane / Q000276:immunology; D004133:Diminazene / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005921:Glomerulonephritis / Q000209:etiology*; D007678:Kidney Glomerulus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D014353:Trypanosomiasis, African / Q000150:complications* / Q000276:immunology / Q000473:pathology
D000906:Antibodies; C003915:diminazene aceturate; D004133:Diminazene