INTEGRATING FUNCTIONAL SINGLE-CELL MULTI-OMICS AND MOLECULAR PATHOLOGY: UNVEILING NOVEL IMMUNE LANDSCAPE SIGNATURES IN SYSTEMIC AUTOIMMUNE PATHOGENESIS

Abstract

Systemic autoimmune diseases (SADs) are characterized by complex immune dysregulation and heterogeneous clinical manifestations, yet their underlying mechanisms remain poorly understood. This study applies an integrative single-cell multi-omics approach, combining single-cell RNA sequencing, epigenomic profiling, and spatial transcriptomics with molecular pathology to investigate immune landscape signatures across SADs, including systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis. The analysis identifies key immune cell subpopulations, such as cytotoxic CD8⁺ T cells, interferon-responsive myeloid cells, and profibrotic monocytes, associated with disease progression. Regulatory network analysis reveals the involvement of interferon and TGF-β signaling pathways in driving immune dysfunction. Spatial mapping further demonstrates that these immune populations localize within distinct tissue niches and interact with stromal cells. Importantly, integrated multi-omic signatures show improved predictive capacity for disease activity. These findings provide a framework for biomarker discovery and precision therapeutic strategies in systemic autoimmune diseases.