A central role of nucleosomes in lupus nephritis.

Lupus nephritis is characterized by the presence of subendothelial and subepithelial immune complexes and thickening of the glomerular basement membranes (GBM). Electron-dense structures (EDS) in mesangium and GBM have been demonstrated to constitute target structures for nephritogenic autoantibodies in vivo. Whether these antibodies bind nucleosomal antigens within the EDS or cross-react with components of the GBM has not been resolved. Data recently published point at intra-GBM-associated nucleosomes as target for the nephritogenic autoantibodies. Colocalization IEM has demonstrated that autoantibodies and experimental antibodies against DNA, histones, or transcription factors like TATA box-binding protein colocalize in the EDS. By using terminal transferase in situ nick-end labeling in combination with immune electron microscopy to detect DNA specifically in human and murine SLE kidneys, we were able to detect DNA within the EDS of nephritic glomeruli that corresponded with the detected autoantibodies.