Serum interferon-beta level determined by an ultrasensitive electrochemiluminescence immunoassay is increased in clinically active and inactive systemic lupus erythematosus

Type I interferons, which play an important role in the pathogenesis of various autoimmune diseases such as systemic lupus erythematosus (SLE), are expressed at very low levels under physiological conditions. In this study, we focused on IFN-beta (IFN) β-for its potential use as a biomarker of SLE activity and compared three different technologies for its quantification in the serum of healthy donors and patients with SLE. A total of 93 serum samples from healthy donors and 463 serum samples from lupus patients were tested using either ELISA, digital ELISA based on Single Molecule Array (Simoa®) technology, or a novel ultrasensitive immunoassay (S-Plex®) based on electrochemiluminescence. Circulating IFNβ- levels were detected in 1.3%, 6.7%, and 100% of healthy donors by Simoa, ELISA, and S-Plex technology, respectively. In patients with SLE, circulating IFNβ- levels were detected in 7.5%, 18.8%, and 98.3% by Simoa, ELISA, and S-Plex technology, respectively, demonstrating the utility of the S-Plex technology for quantifying this cytokine in serum. S-Plex-determined serum IFNβ- concentrations were higher in patients with SLE than in healthy donors (median, 0.297 pg/mL vs 0.205 pg/mL, p=0.0004, respectively), in patients with active SLE compared to those with inactive SLE (0.389 pg/mL vs 0.243 pg/mL, p=0.0013, respectively), in patients with severe flare compared to those without flare (0.462 pg/mL vs 0.244 pg/mL, p=0.0009, respectively), and in patients not in remission compared to those in remission (0.374 pg/mL vs 0.239 pg/mL, p=0.0027, respectively). However, according to ROC curve analyses, S-Plex- determined serum IFNβ- levels demonstrated poor diagnostic performances for distinguishing disease clinical status in SLE. Using S-Plex technology, circulating IFNβ- levels are quantifiable in the serum of healthy donors and are significantly higher in patients with SLE. They increase significantly in patients with clinically active disease. Although IFNβ- is a biomarker of SLE activity, its serum levels in patient groups show considerable overlap, making it difficult to reliably distinguish between different states of disease activity.