Kidney Week

Abstract: TH-OR072

Epitope Mapping of Nephrin Autoantibodies in Diffuse Podocytopathies

Session Information

• Glomerular Diseases: Epidemiology and Real-World Outcomes
  October 22, 2026 | Location: Room 501, Convention Center
  Abstract Time: 05:50 PM - 06:00 PM

Category: Glomerular Diseases

• 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics

Authors

• Shirai, Yoko, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Yoko Shirai, MD, PhD

• Miura, Kenichiro, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Kenichiro Miura, MD, PhD

• Tanabe, Kenji, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Kenji Tanabe, PhD

• Horita, Shigeru, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Shigeru Horita, MD

• Abe, Mayumi, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Mayumi Abe, PhD

• Ban, Hideki, Kumamoto Sekijuji Byoin, Kumamoto, Kumamoto Prefecture, Japan

Hideki Ban

• Goto, Shin, Niigata Daigaku, Niigata, Niigata Prefecture, Japan

Shin Goto, MD, PhD

• Yamamoto, Suguru, Niigata Daigaku, Niigata, Niigata Prefecture, Japan

Suguru Yamamoto, MD, PhD

• Hattori, Motoshi, Tokyo Joshi Ika Daigaku, Shinjuku, Tokyo, Japan

Motoshi Hattori, MD, PhD

Background

Anti-nephrin autoantibodies have been reported as pathogenic circulating factors inducing proteinuria in diffuse podocytopathies including steroid-sensitive nephrotic syndrome (SSNS) and post-transplant recurrent focal segmental glomerulosclerosis (rFSGS) (Watts AJB et al. J Am Soc Nephrol. 2022; Hattori M et al. Am J Transplant. 2022; Shirai Y et al. Kidney Int. 2024). However, the epitopes of nephrin recognized by anti-nephrin autoantibodies remain unclear.

Methods

Stored plasma/serum samples from 13 patients with rFSGS and 6 patients with SSNS who were positive for anti-nephrin autoantibodies were analyzed. Fifty-seven candidate peptides identified using the Immune Epitope Database were synthesized from the extracellular domain (ECD) of nephrin, divided into overlapping 10-amino-acid peptides, and immobilized on ELISA plates. Epitope mapping was performed using an ELISA-based method. 6 cases who had high but below cut-off value anti-nephrin antibody titers among 13 patients with membranous nephropathy and 13 healthy individuals were used as negative controls.

Results

All patients with rFSGS and SSNS had IgG recognizing at least one epitope, whereas sera from control cases did not bind any epitopes. A single epitope (aa78-91) located within the Ig-like C2-type 1 (Ig1) domain was recognized by plasma/sera from all patients with rFSGS and SSNS. IgG recognizing another epitope within the Ig1 domain was detected in all patients with SSNS but in none of the patients with rFSGS. Conversely, IgG recognizing an epitope within the Ig2 domain was detected in all patients with rFSGS but in none of the patients with SSNS.

Conclusion

All patients with rFSGS and SSNS in this study possessed IgG recognizing an epitope located within the Ig1 domain of nephrin. Further investigation is needed to clarify the significance of distinct shared epitope recognition sites in SSNS and rFSGS, respectively.

Funding

• Government Support – Non-U.S.