Elsevier

Clinical Immunology

Volume 124, Issue 2, August 2007, Pages 109-118
Clinical Immunology

Short Analytical Review
Experimental anti-GBM disease as a tool for studying spontaneous lupus nephritis

https://doi.org/10.1016/j.clim.2007.05.007Get rights and content

Abstract

Lupus nephritis is an immune-mediated disease, where antibodies and T cells both play pathogenic roles. Since spontaneous lupus nephritis in mouse models takes 6–12 months to manifest, there is an urgent need for a mouse model that can be used to delineate the pathogenic processes that lead to immune nephritis, over a quicker time frame. We propose that the experimental anti-glomerular basement membrane (GBM) disease model might be a suitable tool for uncovering some of the molecular steps underlying lupus nephritis. This article reviews the current evidence that supports the use of the experimental anti-GBM nephritis model for studying spontaneous lupus nephritis. Importantly, out of about 25 different molecules that have been specifically examined in the experimental anti-GBM model and also spontaneous lupus nephritis, all influence both diseases concordantly, suggesting that the experimental model might be a useful tool for unraveling the molecular basis of spontaneous lupus nephritis. This has important clinical implications, both from the perspective of genetic susceptibility as well as clinical therapeutics.

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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