Abstract

Loss of renal DNase I leads to progression of lupus nephritis. Therefore, we determined if loss of renal DNase I reflects a concurrent loss of urinary DNase I, and whether absence of urinary DNase I predicts disease progression, which thus may reduce the need for renal biopsies. Here, mouse renal DNase I mRNA was determined by qPCR, whereas mouse and human DNase I protein and DNase I endonuclease activity levels were determined by Western blots, and gel and radial zymography assays, respectively, during different stages of the murine and human forms of the disease. Cellular localization of DNase I was analysed by immunohistochemistry, immunofluorescence, confocal microscopy and immune electron microscopy. We further compared DNase I levels in human native and transplanted kidneys to determine if the disease depended on autologous renal genes, or whether the nephritic process proceeded also in transplanted kidneys. We also analysed if DNase I levels in urine samples reflected expression levels in the kidneys, and if the mouse data were translatable to humans.

The data indicates that silencing of the renal DNase I gene expression level relates to serious progression of lupus nephritis in murine, human native, and transplanted kidneys. Notably, silencing of renal DNase I correlates with loss of DNase I protein and endonuclease activity in the urine samples. Thus, urinary DNase I levels reflects the renal DNase I expression and activity levels, and may therefore be used as a marker of lupus nephritis disease progression and reduce the need for renal biopsies.