Interferon levels and interferon-stimulated gene expression identify patient subsets with distinct clinical and immunological characteristics in systemic lupus erythematosus

Introduction: Interferon(IFN) system is dysregulated in Systemic Lupus Erythematosus(SLE) and represents potential therapeutic target. However, most studies have focused on isolated IFN types, particularly type I and type II, while type III IFNs remain poorly characterized. Comprehensive analysis of different IFN types in parallel with interferon-stimulated gene(ISG) expression is limited despite the interconnectedness of IFN families and their potential to differentially influence disease activity, immune phenotypes, and treatment responses. The present study assessed levels of IFN types and IFN score to evaluate their association with disease activity, clinical manifestations, and autoantibody profile in SLE patients from Western India. Methods: This cross-sectional study included clinically diagnosed SLE patients(n=115). Serum IFNα and IFNλ1-λ4 levels were detected using ELISA, while IFNγ levels were detected using bead-based assay, and IFN score by RT-qPCR based on the expression of five ISGs. SLE patients with IFN levels above third quartile were categorized as 'IFN high' groups, and their association with clinical and autoantibody profile were analysed using logistic regression. To identify patient subgroups based on autoantibody profile, unsupervised clustering was employed. Results: SLE patients showed significantly elevated IFNα(p