Autoimmunity: Molecular Mechanisms, Biomarkers, and Therapeutic Opportunities.

Autoimmune diseases (ADs) arise from the breakdown of immune tolerance, yet their clinical course, organ involvement, and treatment responses vary markedly across systemic and organ-specific autoimmune disorders. This diversity cannot be explained by a single pathogenic mechanism or by conventional serological categories alone. Here, we synthesize evidence that autoimmunity is shaped by interacting molecular and cellular regulatory layers, including immunometabolic rewiring, epigenetic remodeling, posttranscriptional regulation, and functional reprogramming of immune and tissue-resident cells. These processes influence pathogenic T-cell and B-cell differentiation, myeloid activation, stromal and epithelial dysfunction, tissue-specific inflammation, and intercellular communication. We further discuss how multidimensional readouts, including metabolites, methylation and chromatin signatures, RNA-based markers, and reprogrammed immune-cell phenotypes, may support diagnosis, disease-activity assessment, prognosis, and therapeutic stratification. From a therapeutic perspective, this framework supports a shift from broad immunosuppression toward mechanism-matched interventions targeting metabolic vulnerabilities, epigenetic regulators, RNA-control pathways, and pathogenic cellular states, including emerging cell-based approaches. We propose that ADs can be viewed as dynamic network disorders in which molecular mechanisms, biomarkers, and therapeutic opportunities are closely connected. Integrating longitudinal multiomics, single-cell and spatial profiling, and standardized biomarker validation may help translate autoimmune heterogeneity into actionable precision-medicine strategies for more individualized care.