Interferons Dominate Damage and Activity in Juvenile Scleroderma.

ABSTRACT

Juvenile scleroderma is a heterogeneous group of diseases associated with sclerotic skin lesions, grouped as juvenile systemic sclerosis systemic sclerosis) and juvenile localized scleroderma. This study aims to measure the cytokine and chemokine levels involved in interferon signaling in patients with juvenile scleroderma and determine their correlation with disease severity. METHOD: Twenty-nine juvenile localized scleroderma five juvenile systemic sclerosis, and nine healthy controls were included in the study. Patients with juvenile localized scleroderma were scored according to the LoSAI (LoSCAT activity index), LoSDI (LoSCAT damage index), and PGA-A (physician global assessment-activity) indices. Cytokines and chemokines involved in interferon gene signaling (IL-1, IL-6, IL-8, IP-10, MCP1, TNF-α, CXCL-11, IFN-α, IFN-ß, IFN-γ) and interferon-stimulated genes (ISGs) including IFI27, IFI44, ISIG15, IFIT1, OAS1, RSAD2 were measured by ELISA and RT-PCR method respectively. RESULTS: A significant increase in IFN-α, IFN-ß, IFN-γ, TNF-α, IL -1, IL -6 IL -8, IP-10, and MCP1 levels was observed in patients with juvenile systemic sclerosis compared with the healthy control group. Furthermore, IFN- α and IP-10 were elevated in both juvenile localized scleroderma and juvenile systemic sclerosis compared to the healthy control group. IFN-γ and IFN-α positively correlated with LoSAI and LoSDI levels, respectively. According to PGA-A analysis, IFN-ß, IFN-γ, TNF-α, IL -8, IP10, MCP1, and CXCL11 were significantly higher in active disease than in the inactive state in both groups. CONCLUSION: The results suggest that interferon signaling may be impaired in patients with juvenile scleroderma. Significant changes were observed in cytokines and genes related to IFN signaling, which may have a crucial role in monitoring disease activity. In addition, we have gained important insights into the possibility of using IFN-α and IFN-γ as biomarkers for monitoring juvenile scleroderma activity and damage.