Glomerular targets of nephritogenic autoantibodies in systemic lupus erythematosus

Transgenic overexpression of anti-double-stranded DNA autoantibody and activation of Toll-like receptor 4 in mice induce severe systemic lupus erythematosus syndromes

“…Although changes in the titers of these autoantibodies may reflect disease activity, their role in lupus pathogenesis remains unclear. These antibodies may bind to DNA or nucleosomes to form circulating ICs and the deposition of these complexes in the tissue may elicit inflammation [1,19,20]. In addition, a subset of pathogenic anti-dsDNA has been shown to penetrate living cells and derange the cell functions in vitro [4,13,21,22].…”

Anti-alpha-actinin antibodies are part of the anti-cell membrane antibody spectrum that characterize patients with lupus nephritis

“…Moreover, the absence of any relationship between anti-MbA and anti-dsDNA Ab or antiC1q Ab suggests distinct, and probably complementary, mechanisms for these different nephritogenic autoAb. Indeed, anti-dsDNA Ab are suspected to deposit in the mesangial matrix (MM) of the glomeruli and to deposit, as the disease progresses, in the glomerular basement membrane (GBM) [28]. Anti-dsDNA Ab bind predominantly to exposed chromatin fragments released from apoptotic cells to form immune complexes present within electrondense structures in the MM and GBM [29].…”

Autoantibodies: Focus on anti-DNA antibodies

“…50,51 However, more recent work shed light on this and suggest that at least some of the reported cross-reactivity can be explained by an indirect binding via nucleosomes. 52 It appears that when anti-DNA antibodies cross-reactive to HS proteoglycans (HSPG) are treated with DNase I, the binding to HSPG is abolished. More detailed analysis revealed that the anti-DNA antibodies bound nucleosomes, derived from the dying hybridoma cells and the binding to HSPG was mediated by these nucleosomes.…”