シライ　ヨウコ   白井　陽子    所属   医学部 医学科（東京女子医科大学病院）    職種   助教
言語種別	英語
発表タイトル	A Possible Role of Anti-Nephrin Autoantibody in Endocytosis of Nephrin in Patients With Post-Transplant Focal Segmental Glomerulosclerosis Recurrence and Minimal Change Disease
会議名	KIdney Week 2022.
主催者	American Society of Nephrology
学会区分	国際学会及び海外の学会
発表形式	口頭
講演区分	一般
発表者・共同発表者	◎白井 陽子
発表年月日	2022/11/05
国名	アメリカ合衆国
開催地 （都市, 国名）	オーランド
開催期間	2022/11/03～2022/11/06
概要	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.