Given that recent data in irf5−/− mice reveal a critical role for IRF5 in regulating TLR-mediated proinflammatory cytokines IL6, TNFα, and IL12 [13], which have been shown, along with IFNα, to be pathologically elevated in the circulation of SLE patients [43]–[45], we performed a comparative analysis of human promoter transactivation by the top four most abundant isoforms. This evidence concerns the gene IRF5 and systemic lupus erythematosus.