By analyzing the correlation between 5 ISGs expression levels and basic or clinical characters, we found that there was a negative correlation between expression levels of ISGs (RSAD2, USP18, IFI44, and ISG15) and the age of SLE patients, while this correlation was not observed in HCs, implying that higher IFN signature might be associated with the pathogenesis of younger SLE patients. Here, ISG15 is linked to systemic lupus erythematosus.