Abstract: FR-PO825
Establishment of Human IgG Autoantibodies Derived from Patients with Lupus Nephritis and Deposition of Resultant Human IgG-Containing Immune Complexes in the Kidney and Skin of Mice
Session Information
- Glomerular Diseases: Inflammation and Immunology
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Ka, Shuk-Man, Department of Medicine, National Defense Medical Center, Taipei, Taiwan
- Chen, Ann, Department of Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
Background
In Taiwan, lupus nephritis (LN) has a trend of 4.3–13.4% rate of progression to end-stage renal disease (ESRD). Treatment for LN mainly relies on glucocorticoids and other immunosuppressants, but targeting more specific pathogenic molecules from the upstream pathways involved in the development and progression of the disease, e.g., etiological autoantibodies (autoAbs), is crucial and remains a unmet medical need.
Methods
We have recently established a human hybridoma platform to generate two human IgG against dsDNA autoantibodies (autoAbs) using peripheral blood mononuclear cells (PBMCs) from LN patients (LiuK-NDMC-01 and LiuK-NDMC-02) to which we performed sequencing and tests for capacity of inducing inflammatory responses and deposition of immune complexes (ICs) in the kidney and skin of ASID mice that mimics the human disease.
Results
By injecting intravenously a single dose of the LiuK-NDMC-01 autoAb against dsDNA and human dsDNA extracted from a human THP-1 monocyte cell line, renal deposition of the human IgG-containing ICs in ASID mice was induced. Immunofluorescence examination showed deposition of human IgG and C3 diffusely in the kidney and IgG in the skin. This effect was also confirmed by a Western blot analysis using renal proteins extracted from the ASID mice. Moreover, increased NLRP3 inflammasome-mediated IL-1β secretion was observed in human macrophages that were primed with the ICs containing the LiuK-NDMC-01 autoAb and dsDNA compared with saline-control counterparts.
Conclusion
Collectively, two new human IgG autoantibodies were established using PBMCs from LN patients. One of these human IgG autoAb was further validated for deposition of the IgG-containing ICs in both the kidney and skin, mimicking LN patients. The ICs was shown to induce inflammatory reaction as demonstrated by resultant activation of NLRP3 inflammasome and subsequent IL-1β secretion in human macrophages.
Funding
- Government Support – Non-U.S.