Interferon profiling identifies clinically distinct endotypes to guide interferon-targeted therapies in systemic lupus erythematosus

The interferon (IFN) system is dysregulated in systemic lupus erythematosus (SLE) and represents a potential therapeutic target. However, SLE heterogeneity poses a major challenge for precision medicine–based disease management. 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 aimed to comprehensively assess IFN levels and the IFN score to evaluate their association with disease activity, clinical manifestations, and autoantibody profiles, in order to define clinically meaningful subsets of SLE and guide interferon-targeted therapeutic strategies.