Lupus glomerulonephritis revisited 2004: autoimmunity and end-organ damage.
Histopathology of the kidney and clinical presentation are critical factors in the diagnosis of immune-mediated glomerulonephritis (GN). The histological manifestations of glomerular injury are shared by multiple underlying mechanisms. Work from our laboratory and from other investigators shows that antinuclear, antihistone or anti-dsDNA antibodies are neither required nor sufficient for development of lupus GN. In addition, antibody to dsDNA can be generated by mechanisms other than loss of tolerance to chromatin. Genetic analyses demonstrate that although there is some interaction between autoantibody production and renal disease, the phenotypes are regulated by distinct genetic intervals. Furthermore, renal failure is not an essential outcome of the immune-complex deposition and proliferative lupus GN. These data are also supported by published studies from systemic lupus erythematosus (SLE) patients. The immune regulation of lupus GN is distinct from other organ-specific diseases and not influenced by CD25(+) or NK1.1(+) regulatory T cells. Thus, fatal GN may depend upon a kidney-reactive T-cell response that, in turn, may be regulated by gender and intrinsic end-organ factors. The data discussed in this review call for a re-evaluation of the current paradigms for pathogenesis of SLE. An interactive model separating autoimmunity from end-organ susceptibility for the pathogenesis of SLE is proposed.
Bagavant
H
H
The University of Virginia Specialized Center of Research on Systemic Lupus Erythematosus, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Deshmukh
U S
US
Gaskin
F
F
Fu
S M
SM
D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D004247:DNA / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000974:Antibodies, Antinuclear; D004247:DNA