Autoantibody repertoire in lupus nephritis: from pathogenic mechanisms to clinical integration for precision decision-making

Lupus nephritis (LN) represents the most severe renal manifestation of systemic lupus erythematosus (SLE), and timely, risk-stratified intervention is essential to mitigate irreversible kidney damage and improve long-term clinical outcomes. The autoantibody repertoire not only constitutes a cornerstone of SLE diagnosis but also serves as a critical pathogenic link between systemic immune dysregulation and site-specific renal injury. This review synthesizes current evidence on established and emerging autoantibodies associated with LN, with an emphasis on their pathogenic contributions to three central mechanisms: immune complex deposition, complement system activation, and direct podocyte injury. We critically evaluate the clinical validity and utility of conventional serological markers, including anti-dsDNA and anti-C1q antibodies, for diagnosing LN, monitoring disease activity, and predicting renal flares or progression, while also elucidating the significance of distinct clinical phenotypes such as the antiphospholipid antibody profile. Furthermore, we discuss strategies for integrating multiple autoantibody indices to construct predictive models, as well as the application prospects of novel technologies enabling non-invasive liquid biopsy. Finally, the challenges and future directions of autoantibody-guided individualized therapy are discussed, with the goal of advancing precision clinical decision-making for LN.