| Summary: | <i>Background and objects:</i> In systemic lupus erythematosus, circulating immune complexes activate complement and, when trapped in renal capillaries, cause glomerulonephritis. Mouse models have been used in the preclinical assessment of targeting complement activation pathways to manage chronic inflammation in lupus. Properdin is the only known positive regulator of complement activation, but its role in the severity of lupus nephritis has not been studied yet. <i>Materials and Methods:</i> Fully characterized properdin-deficient mice were crossed with lupus prone MRL/<i>lpr</i> mice on C57Bl/6 background. <i>Results:</i> Compared to MRL/<i>lpr</i> properdin wildtype mice, MRL/<i>lpr</i> properdin-deficient mice had significantly lower anti-DNA antibody titres, TNFα and BAFF levels in serum. The qualitative glomerulonephritic score was less severe and there was significantly less serum creatinine in MRL/<i>lpr</i> properdin-deficient mice compared to MRL/<i>lpr</i> properdin wildtype littermate mice. <i>Conclusion:</i> Properdin plays a significant role in the severity of lupus overall and specifically in the extent of glomerulonephritis observed in MRL/<i>lpr</i> mice. Because MRL/<i>lpr</i> properdin-deficient mice had lower levels of anti-DNA antibodies, inflammatory mediators and markers of renal impairment, the study implies that properdin could constitute a novel therapy target in lupus disease.
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