Experimental autoimmune Goodpasture's disease: a pathogenetic role for both effector cells and antibody in injury.
BACKGROUND
Goodpasture's disease [antiglomerular basement membrane (GBM) glomerulonephritis] is a classic autoimmune disease and the only organ-specific autoimmune renal disease in which the antigen is well described. The importance of antibodies against the non-collagenous domain of the alpha3 chain of type IV collagen [alpha3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury.


METHODS
Active experimental autoimmune glomerulonephritis (EAG) was induced by immunization with alpha3-alpha5(IV)NC1 heterodimers in B cell intact C57BL/6 mice and B cell (mu chain-deficient) mice. Passive disease was induced by transferring sera from B cell intact and B cell deficient mice with EAG to RAG-1-/- mice (that lack adaptive immunity). Histologic and functional injury was studied.


RESULTS
Despite the absence of B cells and immunoglobulin in B-cell-deficient mice, histologic and functional injury developed in mice immunized with alpha3-alpha5(IV)NC1, with T cells and macrophages in glomeruli. Injury occurred to a similar degree to that found in B-cell-intact mice. Transfer of sera from B-cell-intact mice with EAG containing antibodies (but not from B-cell-deficient mice with EAG) to RAG-1-/- mice induced linear immunoglobulin deposits on the glomerular basement membrane (GBM) and pathologic proteinuria.


CONCLUSIONS
Both cell-mediated and humoral effectors are capable of inducing renal injury in EAG. Given the similarity of the disease-initiating antigen in this model to the antigen in human anti-GBM glomerulonephritis, similar overlapping mechanisms are likely to operate in human disease.
Dean
Elizabeth G
EG
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia.
Wilson
Gabrielle R A
GR
Li
Ming
M
Edgtton
Kristy L
KL
O'Sullivan
Kim M
KM
Hudson
Billy G
BG
Holdsworth
Stephen R
SR
Kitching
A Richard
AR
D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000209:etiology* / Q000276:immunology; D000906:Antibodies / Q000502:physiology* / Q000633:toxicity; D001323:Autoantibodies; D001402:B-Lymphocytes / Q000502:physiology*; D005921:Glomerulonephritis / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011507:Proteinuria / Q000209:etiology
D000906:Antibodies; D001323:Autoantibodies; C051951:antiglomerular basement membrane antibody