Abstract: FR-PO817
Clinical Evidence That Defines IgAN as a Tissue-Specific Autoimmune Glomerulonephritis
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
- Nihei, Yoshihito, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Koizumi, Ayako, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Barratt, Jonathan, Leicester General Hospital, Leicester, United Kingdom
- Suzuki, Hitoshi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
Background
IgA nephropathy (IgAN) is thought to be mediated by immune complexes containing galactose-deficient IgA (Gd-IgA1) and antigen specificity of glomerular IgA has not been emphasized in the pathogenesis of IgAN. However, we recently reported that IgA-type autoantibodies against mesangial cells (anti-β2-spectrin and anti-CBX3 IgA) were detected in the sera of IgAN model mice (Sci. Adv. 2023. Life Sci. Alliance 2024). Here, we aimed to show clinical evidence of these IgA autoantibodies in human IgAN.
Methods
Patients with biopsy-proven IgAN (n=119) and the other kidney disease (DC: disease control, n=51) were recruited from Juntendo University Hospital in Japan (70 IgAN and 32 DC patients) or Leicester General Hospital in the UK (49 IgAN and 19 DC patients). Serum anti-β2-spectrin and anti-CBX3 IgA were measured by ELISA. Glycosylation of purified anti-β2-spectrin and anti-CBX3 IgA were analyzed by western blot (WB) using anti-Gd-IgA1 antibody.
Results
Anti-β2-spectrin and anti-CBX3 IgA were more frequently detected in patients with IgAN than DC in both Japan and the UK cohort (Figure 1). Overall, 30 of 119 IgAN and 3 of 51 DC patients were positive for anti-β2-spectrin IgA (sensitivity, 25.2%; specificity, 94.1%), while 48 of 119 IgAN and 3 of 51 DC patients were positive for anti-CBX3 IgA (sensitivity, 40.3%; specificity, 94.1%). Sixteen IgAN patients were positive for both anti-β2-spectrin and anti-CBX3 IgA. WB analysis revealed that the purified serum anti-β2-spectrin and anti-CBX3 IgA from IgAN patients were enriched for Gd-IgA1 than the total serum IgA (Figure 2).
Conclusion
The anti-β2-spectrin and anti-CBX3 IgA are detected in IgAN patients with high specificity. Furthermore, these IgA-type autoantibodies have the property of galactose deficiency, namely, anti-mesangium Gd-IgA1 are present in circulation of IgAN patients. Thus, we provide clinical evidence that anti-mesangium IgA is involved in the pathogenesis of human IgAN and defines IgAN as a tissue-specific autoimmune glomerulonephritis.
Funding
- Government Support – Non-U.S.