Serum high-mobility group box 1 is correlated with interferon-α and may predict disease activity in patients with systemic lupus erythematosus

Abstract

Sensing self-nucleic acids through toll-like receptors in plasmacytoid dendritic cells (pDCs), and the dysregulated type I IFN production, represent pathogenic events in the development of the autoimmune responses in systemic lupus erythematosus (SLE). Production of high-mobility group box-1 protein (HMGB1) promotes type I IFN response in pDCs. To better understand the active pathogenic mechanism of SLE, we measured serum levels of HMGB1, thrombomodulin, and cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17A, IL-17F, IFNα, IFNγ, TNFα) in 35 patients with SLE. Serum HMGB1 and IFNα were significantly higher in patients with active SLE (SLE Disease Activity Index (SLEDAI) score ≥ 6) compared with healthy donors or patients with inactive SLE. Furthermore, the HMGB1 levels were significantly correlated with IFNα levels. By qualitative analysis, the detection of serum IFNα or HMGB1 suggests active SLE and the presence of SLE-related arthritis, fever, and urinary abnormality out of SLEDAI manifestations. Collectively, HMGB1 and IFNα levels are biomarkers reflecting disease activity, and qualitative analysis of IFNα or HMGB1 is a useful screening test to estimate SLE severity and manifestations. Our results suggest the clinical significance of type I IFNs and HMGB1 as key molecules promoting the autoimmune process in SLE.

Serum interleukin-6 level is correlated with the disease activity of systemic lupus erythematosus: a meta-analysis

“…A total of 13 studies compared the serum IL-6 levels between SLE patients and healthy controls (23)(24)(25)(27)(28)(29)(32)(33)(34)39,40,43,46). Serum IL-6 levels between active and inactive SLE patients were compared in 9 studies (24)(25)(26)29,31,39,(41)(42)(43). Additionally, the correlation coefficient between serum IL-6 level and SLE disease activity was reported in 13 studies (24)(25)(26)(29)(30)(31)(35)(36)(37)(38)(39)44,45).…”

“…Additionally, the correlation coefficient between serum IL-6 level and SLE disease activity was reported in 13 studies (24)(25)(26)(29)(30)(31)(35)(36)(37)(38)(39)44,45). Among all included studies, 3 studies focused on children with SLE (25,28,46), and 21 studies focused on adults with SLE (23,24,26,27,(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45). The NOS scores for the included studies ranged from six to seven, indicating that they were of moderate to high quality and suitable for pooled analysis.…”

“…A total of nine studies compared the serum IL-6 levels between patients with active SLE and inactive SLE (24)(25)(26)29,31,39,(41)(42)(43). The random-effects model was used to perform the pooled analysis due to the significant heterogeneity (I 2 =96%, po0.01).…”

Extracellular HMGB1: a therapeutic target in severe pulmonary inflammation including COVID-19?

“…Active HMGB1 release is initiated with a regulated translocation of the nuclear pool of HMGB1 to the cytosol (Bonaldi et al 2003). Type 1 and type 2 interferons are highly potent endogenous molecules that launch this intracellular relocalization of HMGB1 (Lu et al 2014;Tanaka et al 2019). Consequently, administration of interferons as therapeutic antiviral compounds risks to increase extracellular HMGB1 levels, which may promote inflammation rather than mediate beneficial effects.…”

HMGB1 in Systemic Lupus Erythematosus

“…Oxidative stress is known to be increased in SLE and contributes to immune system dysregulation (24) and it is likely that partially oxidized, disulfide HMGB1 contributes to this process. Serum HMGB1 is elevated in SLE patients and levels of serum HMGB1 correlate with disease activity (25). The present review discusses the role of HMGB1 as a DAMP in both the innate and the adaptive aspects of SLE pathogenesis (Figure 1).…”