Abstract: FR-PO801
Serial Changes of Molecular Expression of Slit Diaphragm Proteins in Post-transplant FSGS Recurrence Associated with Anti-nephrin Antibodies
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
- Shirai, Yoko, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
- Miura, Kenichiro, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
- Taneda, Sekiko, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
- Honda, Kazuho, Showa Daigaku, Shinagawa-ku, Tokyo, Japan
- Tanabe, Kenji, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
- Hattori, Motoshi, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
Background
Recently, we reported very early pathological changes in podocytes in patients with post-transplant recurrence of focal segmental glomerulosclerosis (rFSGS) associated with circulating anti-nephrin antibodies (abs), suggesting that anti-nephrin abs are a possible candidate for circulating factors involved in the pathogenesis of rFSGS (Hattori et al, Am J Transplant, 2022; Shirai et al, Kidney Int, 2024). Here, we analyzed serial changes of molecular expression of slit diaphragm proteins in post-transplant FSGS recurrence associated with anti-nephrin abs, using serial graft biopsies.
Methods
We analyzed four kidney transplant recipients with childhood-onset primary FSGS who had positive circulating anti-nephrin abds and underwent serial graft biopsies including 1 hour graft biopsy (1hGBx). All patients underwent whole exome sequencing and no pathogenic variants in FSGS-related genes were identified. Dual immunofluorescence staining images of IgG and nephrin, CD2-associated protein (CD2AP), and podocin were obtained using the structured illumination microscopy.
Results
In all 4 rFSGS patients, 1hGBx showed punctate IgG deposition co-localizing with nephrin that had altered distributions from foot process to podocyte intracellular area. CD2AP was diffusely expressed in podocyte cell bodies before re-perfusion, and 1hGBx showed granular aggregation of CD2AP. In graft biopsies during recurrence (rGBx) obtained at median POD 38 (IQR, 18, 55), the expression of nephrin and CD2AP was decreased in all patients. In contrast, foot process expression of podocin was neither decreased nor altered in 1hGBx and rGBx specimens of three patients. In the remaining one patient, who did not respond to treatment and rapidly progressed to graft loss, expression of podocin was neither decreased nor altered in 1hGBx, but was decreased without altered localization in rGBx.
Conclusion
Nephrin showed altered distributions from foot process to podocyte intracellular area, and CD2AP showed decreased expression and granular aggregation at very early phase of exposure to anti-nephrin abs. In contrast, podocin localization was not altered even after progression of FSGS recurrence. These findings may contribute to better understanding the mechanism of podocyte injury associated with anti-nephrin abds.
Funding
- Government Support – Non-U.S.