IRF5 and systemic lupus erythematosus: We can infer that the persistent IRF5 hyperactivation in RP-SLE maintains a state of disease “smoldering.” Although the patients with RP-SLE have little or no overt clinical symptoms, IRF5 remains activated in innate immune cells to evoke the production of cytokines, at least a sufficient amount of type I IFNs to induce ISG expression and possibly to promote OXPHOS in mitochondria.