While our study and others49 found that IFN-II plays no role in the IFN signature, as well as disease activity and autoantibodies, and that it has been shown to be an ineffective therapeutic target in SLE,61,62 our data suggest that increased levels of IFN-II are associated with IFN-I-independent transcriptional profiles dysregulated in SLE, including mitochondria, oxidative phosphorylation, and the clonal expansion of CD8+GZMH+ cells.7 Here, IFNA1 is linked to systemic lupus erythematosus.