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Kidney Week

Abstract: TH-PO776

Multi-Institutional Study of Anti-Nephrin Autoantibodies in Post-Transplant Focal Segmental Glomerulosclerosis Recurrence

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Shirai, Yoko, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
  • Miura, Kenichiro, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
  • Ishizuka, Kiyonobu, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
  • Ando, Taro, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
  • Kanda, Shoichiro, Tokyo Daigaku, Bunkyo-ku, Tokyo, Japan
  • Hashimoto, Junya, Toho Daigaku, Ota-ku, Tokyo, Japan
  • Hamasaki, Yuko, Toho Daigaku, Ota-ku, Tokyo, Japan
  • Hotta, Kiyohiko, Hokkaido Daigaku, Sapporo, Hokkaido, Japan
  • Tanabe, Kenji, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
  • Takano, Tomoko, McGill University Faculty of Medicine and Health Sciences, Montreal, Quebec, Canada
  • Hattori, Motoshi, Tokyo Joshi Ika Daigaku, Shinjuku-ku, Tokyo, Japan
Background

Post-transplant recurrence of focal segmental glomerulosclerosis (rFSGS) is a major challenge in kidney transplantation. Recently, we reported very early pathological changes in podocytes and possible roles of circulating anti-nephrin antibodies (abs) in a patient with rFSGS (Hattori et al, Am J Transplant, 2022). To confirm these preliminary results, we performed a multi-institutional study.

Methods

14 Japanese kidney transplant recipients with childhood-onset primary FSGS who had stored plasma samples and graft biopsy specimens were analyzed. All patients underwent whole exome sequencing and no pathogenic variants in FSGS-related genes were identified. Circulating anti-nephrin abs were measured by ELISA and the cut off levels were defined as 231 U/mL, the maximum antibody levels among the controls (9 genetic FSGS patients, 13 membranous nephropathy patients, 4 lupus nephritis patients and 13 healthy controls). Dual immunofluorescence staining of nephrin and IgG or ShcA, an adaptor protein of phosphorylated nephrin, was performed using the structured illumination microscopy.

Results

There were 10 rFSGS and 4 non-recurrent (non-rFSGS) patients. In rFSGS patients, median (interquartile range) anti-nephrin abs before transplant or during a post-transplant recurrence were markedly high at 950 (839, 1323) U/mL. Graft biopsies showed punctate IgG deposition co-localizing with nephrin that showed altered localization and increased expressions of ShcA. Eight of 10 rFSGS patients achieved remission, and graft biopsies after remission showed normal nephrin expression and no signals for IgG and ShcA. Anti-nephrin abs decreased to 261 (121, 398) U/mL in 4 patients with available samples at remission. In non-rFSGS patients, anti-nephrin abs were comparable with the controls regardless of the timing of sample collection. Their graft biopsies showed normal nephrin expression and no signals for IgG and ShcA.

Conclusion

Our results suggest that anti-nephrin abs are associated with rFSGS via nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding and to determine the prevalence and incidence of post-transplant FSGS recurrence associated with anti-nephrin abds.

Funding

  • Government Support – Non-U.S.