Abstract: TH-PO0413
Pathogenic Characterization and Structural Insights of the Human IgG Autoantibodies Identified from Patients with Lupus Nephritis
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Author
- Ka, Shuk-Man, National Defense Medical Center, Taipei City, Taiwan
Background
Autoantibodies that are strongly associated with lupus nephritis (LN) are a type of antinuclear antibody (ANA) that mainly target double-stranded DNA (dsDNA) and play a key role in disease diagnosis and monitoring. These anti-dsDNA antibodies can form immune complexes and deposit in the glomerular and tubular sites of the kidney, which may trigger inflammation activities and complement cascades and even penetrate into renal cells in LN patients.
Methods
In this study, we used a human hybridoma technology to identify two human IgG autoantibodies, LK01 and LK02, from a resident and a non-resident patient respectively.
Results
By analyzing their binding properties with human dsDNA and inflammatory responses in macrophages, LK02 was found to exhibit a higher binding avidity and stronger pro-inflammatory effects. Pathogenicity of lupus nephritis was evaluated in mouse models using immunofluorescence and electron microscopy, revealing substantial IgG deposition and complement activation in renal and skin tissues induced by both autoantibodies, with LK02 consistently showing superior results. The functional difference between two autoantibodies may be attributed to the different length and charge distribution of their HCDR loops. Molecular dynamics simulation was applied to analyze potential key residues involved in DNA binding on the predicted structure of LK02, and site-directed mutagenesis was done for amino-acid substitution, resulting in a modified autoantibody which outperformed the original one in both DNA binding and inflammatory induction.
Conclusion
Overall, this study has detailed the functional and structural profiles of two human LN-related autoantibodies and offered valuable insights that may inspire future research into autoantibody heterogeneity to enhance understanding of SLE pathogenesis.
Funding
- Government Support – Non-U.S.