白井 陽子
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Assistant Professor |
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Language | English |
Title | A Possible Role of Anti-Nephrin Autoantibody in Endocytosis of Nephrin in Patients With Post-Transplant Focal Segmental Glomerulosclerosis Recurrence and Minimal Change Disease |
Conference | KIdney Week 2022. |
Promoters | American Society of Nephrology |
Conference Type | International society and overseas society |
Presentation Type | Speech |
Lecture Type | General |
Publisher and common publisher | ◎白井 陽子 |
Date | 2022/11/05 |
Country | United States |
Venue (city and name of the country) |
オーランド |
Holding period | 2022/11/03~2022/11/06 |
Summary | 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. |