Circulating Interleukin-6 and Janus Kinase 2 DNA Copies in Serum Cell-Free DNA Are Elevated in Patients With Systemic Sclerosis

Recently, cell-free DNA (cfDNA) has gained attention as a diagnostic and prognostic biomarker for various conditions, including autoimmune and inflammatory skin diseases. However, reports of cfDNA use in patients with systemic sclerosis (SSc) are limited. The purpose of this study was to investigate the clinical significance of cfDNA in patients with SSc and assess the circulating DNA levels of key cytokines associated with SSc fibrosis. Serum samples were obtained from 64 patients with SSc, 9 with very early SSc, and 20 healthy controls (HC). Circulating DNA copies were quantified using droplet digital polymerase chain reaction analysis. The DNA copies of interleukin (IL)-6, IL-8, Janus kinase 2 (JAK2), and connective tissue growth factor were significantly higher in patients with SSc than in the HCs. Although not statistically significant, circulating IL-6 DNA copies were higher in patients with SSc than in patients with very early SSc. Receiver operating characteristic analysis indicated that IL-6 DNA copies could distinguish patients with SSc from both the HCs and patients with very early SSc (area under the curve > 0.7 in both cases). Disease type dcSSc and reduced %FVC were significant independent predictors of higher circulating IL-6 and JAK2 DNA copies in multivariate logistic regression analysis. cfDNA, including circulating IL-6 and JAK2 DNA in sera, may serve as valuable indicators for diagnosis and fibrosis progression in patients with SSc.