Convergent nucleic-acid sensing and IFNAR–JAK–STAT signaling, modulated by post-transcriptional control, epigenetic modifications, and non-coding RNAs, yield interferon-stimulated gene signatures that are typically more pronounced in systemic lupus erythematosus and more heterogeneous across rheumatoid arthritis and vasculitis. The gene discussed is IFNAR1; the disease is vasculitis.