Autoantibodies in Systemic Lupus Erythematosus: Diagnostic and Pathogenic Insights

Abstract

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by widespread immune dysregulation and the production of autoantibodies targeting nuclear, cytoplasmic, and cell surface antigens. These autoantibodies are central to disease pathogenesis, contribute to immune complex formation and organ damage, and serve as essential diagnostic and prognostic markers. Their detection supports disease classification, guides clinical decision-making, and offers insight into disease activity and therapeutic response. Traditional markers such as anti-nuclear antibodies (ANA), anti-dsDNA, and anti-Sm antibodies remain diagnostic cornerstones, but growing attention is given to anti-C1q, anti-nucleosome antibodies (ANuA), anti-ribosomal P, antiphospholipid, and anti-cytokine antibodies due to their associations with specific disease phenotypes and activity. These markers may reflect disease activity, specific organ involvement, or predict flares. The mechanisms underlying their persistence include B cell tolerance failure and long-lived plasma cell activity. The aim of this review is to summarize current knowledge on the major autoantibodies in SLE, appraise available detection methods, highlight their clinical utility and limitations and present evidence on the association between antibodies and disease phenotypes.

Keywords: autoantibodies; lupus nephritis; systemic lupus erythematosus; targeted therapies.

Figure 1

Pathophysiologic mechanism of antibody production in SLE. Key events include defective apoptotic debris clearance, neutrophil extracellular trap (NET) formation, and dysregulated type I interferon signaling, which stimulate plasmacytoid dendritic cells and autoreactive B cells via TLRs. B cell tolerance breakdown, excess BAFF signaling, and abnormal T cell help (CD40L, IL-21, ICOS) drive germinal center responses, affinity maturation, and plasma cell formation. Long-lived plasma cells produce high-affinity autoantibodies, perpetuating immune complex formation and chronic inflammation. The cycle is sustained by genetic susceptibility, complement dysfunction, and impaired regulatory T cell control.

Figure 2

Major SLE-related organ manifestations and their corresponding autoantibody associations.