Kidney Week

Abstract: SA-OR25

A Possible Role of Anti-Nephrin Autoantibody in Endocytosis of Nephrin in Patients With Post-Transplant Focal Segmental Glomerulosclerosis Recurrence and Minimal Change Disease

Session Information

• Glomerular Diseases: Mechanisms of Cellular Injury
  November 05, 2022 | Location: W414, Orange County Convention Center‚ West Building
  Abstract Time: 05:06 PM - 05:15 PM

Category: Glomerular Diseases

• 1304 Glomerular Diseases: Podocyte Biology

Authors

• Shirai, Yoko, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Yoko Shirai, MD, PhD

• Miura, Kenichiro, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Kenichiro Miura,

• Kanda, Shoichiro, Department of Pediatrics, Tokyo University, Tokyo, Japan

Shoichiro Kanda,

• Ishizuka, Kiyonobu, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Kiyonobu Ishizuka,

• Ando, Taro, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Taro Ando,

• Nakamura, Misako, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Misako Nakamura,

• Nakatani, Ryo, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Ryo Nakatani,

• Kato, Aya, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Aya Kato,

• Eguchi, Makoto, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Makoto Eguchi,

• Honda, Kazuho, Department of Anatomy, Showa University School of Medicine, Tokyo, Japan

Kazuho Honda,

• Yamaguchi, Yutaka, Yamaguchi Pathology Laboratory, Chiba, Japan

Yutaka Yamaguchi,

• Hattori, Motoshi, Department of Pediatric Nephrology, Tokyo Women’s Medical University, Tokyo, Japan

Motoshi Hattori,

Background

Recently, we have found that in a case with post-transplant focal segmental glomerulosclerosis recurrence (rFSGS), circulating nephrin autoantibody was present in the patient’s serum and altered localization of nephrin, which merged with IgG, was observed in the kidney tissue specimens of postperfusion (1 h) (Hattori, et al. Am J Transplant 2022). To investigate the mechanism of altered localizations of nephrin in rFSGS, we examined whether phosphorylation of nephrin and endocytosis are involved in very early phases of rFSGS using immunofluorescence study.

Methods

1h biopsy specimens obtained from four patients with rFSGS and native kidney biopsy specimens obtained from four patients with minimal change disease (MCD) relapse were analyzed. Double immunostaining of nephrin or phosphorylated nephrin (p-nephrin) (tyr1176) and IgG were performed using structured illumination microscopy. In addition, double immunostaining of nephrin and ShcA, an adapter protein of p-nephrin, or cholera enterotoxin subunit B (CTxB), a marker of raft-mediated endocytosis (RME), were performed using confocal microscope.

Results

Punctate IgG depositions were co-localized with nephrin and p-nephrin (tyr1176) in all patients with rFSGS and three of four patients with MCD relapse. In these seven cases with rFSGS and MCD whose specimens showed punctate IgG deposition co-localizing with nephrin, altered localization of nephrin was observed and the expressions of ShcA were upregulated co-localizing with nephrin. CTxB was colocalized with nephrin in all rFSGS patients, while almost no expression was observed in MCD patients.

Conclusion

Anti-nephrin autoantibodies and phosphorylation of nephrin which is associated with ShcA might be involved in the pathogenesis of very early phases of rFSGS and partly contribute to relapse in a subset of MCD patients. Notably, Our study may also suggest that CTxB relating RME altered localizations of nephrin in rFSGS, but not in MCD.