The described inverse associations between anti-IFI16 positivity, proteinuria, and C3 hypocomplementemia, together with the observation that nephritis does not occur in other systemic autoimmune diseases characterized by high titers of anti-IFI16 antibodies such as SjS and SSc, imply that ultimately these antibodies do not play a relevant role in the pathogenesis of renal inflammation in SLE, but rather most likely prevent complement consumption. This evidence concerns the gene IFI16 and systemic lupus erythematosus.