Tanaka A, et al. - To better appreciate the active pathogenic mechanism of systemic lupus erythematosus (SLE), experts estimated serum levels of high-mobility group box-1 protein (HMGB1, its promotes type I IFN response in plasmacytoid dendritic cells), thrombomodulin, and cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, interferon-α {IFNα}, IFNγ, TNFα) in 35 patients with SLE. In comparison with healthy donors or subjects with inactive SLE, serum HMGB1 and IFNα were notably greater in subjects with active SLE (SLE Disease Activity Index {SLEDAI} score ≥ 6). The significant association amongst the HMGB1 levels and IFNα levels was observed. The discovery of serum IFNα or HMGB1 inferred active SLE and the presence of SLE-related arthritis, fever, and urinary abnormality out of SLEDAI manifestations. Collectively, HMGB1 and IFNα levels were biomarkers that highlighted disease activity, and qualitative analysis of IFNα or HMGB1 was noted to be a valuable screening test to assess SLE severity and manifestations. Hence, the type I IFNs and HMGB1 were concluded as clinically important molecules that promoted the autoimmune process in SLE.