From pathogenesis to precision medicine in systemic lupus erythematosus: Emerging biomarkers and targeted interventions

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by immune dysregulation, autoantibody production, and chronic inflammation, which can potentially damage almost any organ. The estimated worldwide prevalence of SLE ranges from 5 to 7 million, and it is associated with significant morbidity, premature death, and significant global disparities in terms of sex, ethnicity/race, and geography. The key pathological basis of SLE is autoantibody production and the subsequent immune complex-mediated tissue damage, which is the culmina+ abnormal type I interferon signaling, formation of neutrophil extracellular traps, activation of plasmacytoid dendritic cells, imbalance in the homeostasis of T cells and B cells, hyperactivation of B cells, and dysregulated germinal center responses. This review offers a summary of the immunological mechanisms of SLE, encompassing genetic predisposition, epigenetic alterations, and innate and adaptive immune features. In addition, organ-specific manifestations of SLE, including lupus nephritis, neuropsychiatric SLE, cutaneous disease, cardiovascular involvement, hematological involvement, and musculoskeletal sequelae have also been discussed in the context of immune dysregulation. Furthermore, the recent progress in SLE biomarkers, multi-omics integration, and machine learning techniques that allow for molecular stratification and precision medicine have been highlighted. Finally, standard of care treatments, approved biologics, and novel immunotherapies (e.g., CAR-T cell strategies and restoration of immune tolerance), as well as the unmet needs, have been summarized. Altogether, this review integrates the immunological mechanisms with clinical translation to propose a framework for personalized and potentially curative treatment of SLE.