Abstract: TH-PO0716
Analysis of Multiple Autoantibodies in Post-Transplant Recurrent FSGS
Session Information
- Glomerular Innovations: Artificial Intelligence, Multiomics, and Biomarkers
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Shirai, Yoko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan
- Miura, Kenichiro, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan
- Ito, Naoko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan
- Taneda, Sekiko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan
- Koike, Junki, St. Marianna University, Tokyo, Japan
- Honda, Kazuho, Showa Daigaku, Shinagawa, Tokyo, Japan
- Hattori, Motoshi, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan
Background
We previously reported that anti-nephrin autoantibodies (autoAbs) may act as a circulating factor responsible for post-transplant recurrent focal segmental glomerulosclerosis (rFSGS) (Hattori M, et al., Am J Transplant, 2022; Shirai Y, et al., Kidney Int, 2024). Recently, autoAbs targeting slit diaphragm molecules other than nephrin have been described.
Methods
We analyzed 19 cases of rFSGS who underwent kidney transplantation, in which allograft biopsy specimens during recurrence were available. Among these, 10 achieved complete remission, 4 partial remission, and 5 were non-responders. Dual staining of IgG with nephrin, podocin, or Kirrel1 was evaluated by structured illumination microscopy. Anti-nephrin and anti-podocin autoAbs were quantified by ELISA in available plasma samples.
Results
IgG depositions on podocytes were observed in 18 of 19 cases (95%). IgG was co-localized with nephrin, podocin, and Kirrel1 in 15 (79%), 7 (37%), and 10 (53%) cases, respectively (Figure). In all cases with available plasma samples, circulating autoAbs against nephrin and podocin were detected, corresponding to the colocalization of IgG with these molecules. Co-localization of IgG with two or three slit diaphragm molecules was observed in 10 cases (Figure). Notably, nephrin co-localized with IgG exhibited altered localization to the intracellular areas of podocytes, whereas podocin and Kirrel1 remained localized to the slit diaphragm despite IgG binding. No clear correlations were observed between IgG deposition patterns or co-localization profiles and treatment response.
Conclusion
Multiple anti-slit autoAbs were commonly identified in rFSGS. Difference in localizations of slit diaphragm molecules may provide insights into the pathogenesis of rFSGS.
A graphical representation of the frequency of each autoantibody.
Funding
- Government Support – Non-U.S.