Anti-dsDNA Antibodies Promote Initiation, and Acquired Loss of Renal Dnase1 Promotes Progression of Lupus Nephritis in Autoimmune (NZBxNZW)F1 Mice
Figure 5
Anti-dsDNA antibodies and renal Dnase1 levels, and their correlation with EDS in mesangial matrix and GBM, respectively.
Data on Dnase1 mRNA levels and EDS in the mesangial matrix (weighted 1 in Figure 5A and B), or in GBM (weighted 2) where combined for each mouse and sorted by descending Dnase1 mRNA levels. The result of this analysis demonstrates a clear negative correlation between Dnase1 mRNA levels and presence of EDS in GBM. This association was statistically highly significant (A, see Table 1 for statistical analyses). The inverse correlation of EDS in the mesangial matrix with Dnase1 mRNA levels was weaker, and did not reach statistical significance (A, Table 1). The presence of EDS solely in the mesangial matrix was significantly associated with production of anti-dsDNA antibodies (B, Table 1). This demonstrates that deposition of EDS in the mesangial matrix and in the GBM may originate from different molecular processes; EDS in mesangial matrix depend on presence of antibodies to dsDNA, while EDS in GBM depend on reduced renal Dnase1 activity. Production and titers of antibodies to dsDNA was not significantly associated with levels of renal. Dnase1 mRNA and enzyme activities (C, Table 1).