Importantly, our NETs proteome data, coupled with results of ex vivo inhibition assays, implicate NET proteases in the generation of bioactive IL-33 of high interferogenicity, thus offering what we believe are novel mechanistic insights linking neutrophil activation and NETosis with IFN-α and end-organ injury in human SLE. This evidence concerns the gene IFNA1 and systemic lupus erythematosus.