Short Analytical ReviewExperimental anti-GBM disease as a tool for studying spontaneous lupus nephritis
Section snippets
The anti-GBM antibody disease
Anti-GBM antibody disease is a rare autoimmune disorder characterized by the presence of anti-GBM antibodies (Abs) and rapidly progressive crescentic glomerulonephritis. When pulmonary hemorrhage is also present, this condition is usually termed Goodpasture’s syndrome [1]. The disease was firstly described by Ernest Goodpasture in 1919 [2] and later named Goodpasture’s syndrome or Goodpasture’s disease by Stanton and Tange [3] in 1958.
The central pathogenic role of anti-GBM antibody was
Comparison of experimental anti-GBM nephritis and spontaneous lupus nephritis
Table 1 lists some of the differences between experimental GBN and SLN. Whereas anti-GBM antibodies are key in the pathogenesis of GBN, ANA, anti-dsDNA, anti-glomerular and other autoantibodies play important roles in the pathogenesis of SLN [24], [25], [26], [27], [28]. Immune complex deposition plays a secondary or negligible role in the development of GBN. However, in SLN, immune complex deposition at various sites, including glomeruli, tubular and peritubular capillary basement membranes
T cell immunity is required in both disease models
Of interest, T cells appear to play a pathogenic role in both disease settings (Table 2). Early studies already documented that T cells and macrophages infiltrated the glomeruli in GBN [29]. Moreover, these glomerular-infiltrating T cells appeared to be activated as revealed by their expression of interleukin-2 (IL-2) receptor, various T cell cytokines [30] and their proliferation in vitro in response to affinity-purified Goodpasture antigen [31], [32].
The requirement for CD4+ and CD8+ T cells
Molecular mediators affecting both GBN and SLN
Several molecular mediators such as cytokines, chemokines, adhesion molecules and surface receptors have been shown to play essential or important roles in mediating the immunoinflammatory response in both GBN and SLN. They have been summarized in Table 3 and briefly overviewed below. Excluded from this review and Table 3 are molecules for which only the expression data are available in either disease setting. Only the studies where the degree of nephritis has been examined after deliberately
Conclusion
To close, we have briefly compared GBN and SLN, with respect to their underlying pathology as well as their molecular bases. Though the inciting autoantibody, autoantigen, the nature or presence of immune deposits as well as the pathological details may differ in both disease sittings, there is increasing evidence indicating that both diseases share common downstream pathways of disease development. The same set of effector molecules, including complement, pro-inflammatory cytokines,
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