Experimental autoimmune Goodpasture's disease: A pathogenetic role for both effector cells and antibody in injury

Experimental autoimmune Goodpasture's disease: A pathogenetic role for both effector cells and antibody in injury.BackgroundGoodpasture'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 α3 chain of type IV collagen [α3(IV)NC1] is well established. However, observational human studies and studies in experimental systems also imply a role for cell-mediated effector injury.MethodsActive experimental autoimmune glomerulonephritis (EAG) was induced by immunization with α3-α5(IV)NC1 heterodimers in B cell intact C57BL/6 mice and B cell (μ 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.ResultsDespite the absence of B cells and immunoglobulin in B-cell–deficient mice, histologic and functional injury developed in mice immunized with α3-α5(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.ConclusionBoth 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