Oke V, et al. - In a large cohort of 497 patients with systemic lupus erythematosus (SLE), an autoimmune disease that can affect many organ systems, and 322 controls, researchers measured levels of type I, II and III interferons (IFNs) and examined relationships among high levels of different IFN types and distinct SLE features by nominal regression analysis. Findings revealed that high functional type I IFN activity captures active SLE in most domains, but more distinct patterns of organ involvement are linked to circulating IFNs profiles. High IFN-γ and high functional type I IFN activity are characteristic of severe SLE with nephritis and arthritis, while high IFN-α levels are associated with active mucocutaneous inflammation and a more benign cardiovascular profile. A milder disease is associated with IFN-λ1 in isolation. The study findings suggest that IFNs contribute to the heterogeneity of clinical manifestations in SLE, and measuring circulating IFNs may help design clinical trials with therapies that target IFN pathways.