ISG15 and systemic lupus erythematosus: Interestingly, mutations in ISG15 have been found in AGS and, in addition, a higher expression of this gene in SLE patients has been reported in several studies (58–60) ISG15 negatively regulates IFN-alpha and beta production (58), and is known as an activator of natural killer (NK) cells and a driver of IFNγ secretion (61).