A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence.

Yoko Shirai, Kenichiro Miura, Kiyonobu Ishizuka, Taro Ando, Shoichiro Kanda, Junya Hashimoto, Yuko Hamasaki, Kiyohiko Hotta, Naoko Ito, Kazuho Honda, Kenji Tanabe, Tomoko Takano, Motoshi Hattori

Kidney international 2024 Mar

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Possible roles of anti-nephrin anti bodies in post-transplant recurrent focal segmental glomerulosclerosis (FSGS) have been reported recently. To confirm these preliminary results, we performed a multi-institutional study of 22 Japanese pediatric kidney transplant recipients with FSGS including eight genetic FSGS and 14 non-genetic (presumed primary) FSGS. Eleven of the 14 non-genetic FSGS patients had post-transplant recurrent FSGS. Median (interquartile range) plasma levels of anti-nephrin anti bodies in post-transplant recurrent FSGS measured using ELISA were markedly high at 899 (831, 1292) U/mL (cutoff 231 U/mL) before transplantation or during recurrence. Graft biopsies during recurrence showed punctate IgG deposition co-localized with nephrin that had altered localization with increased nephrin tyrosine phosphorylation and Src homology and collagen homology A expressions. Graft biopsies after remission showed no signals for IgG and a normal expression pattern of nephrin. Anti-nephrin antibody levels decreased to 155 (53, 367) U/mL in five patients with samples available after remission. In patients with genetic FSGS as in those with non-genetic FSGS without recurrence, anti-nephrin antibody levels were comparable to those of 30 control individuals, and graft biopsies had no signals for IgG and a normal expression pattern of nephrin. Thus, our results suggest that circulating anti-nephrin anti bodies are a possible candidate for circulating factors involved in the pathogenesis of post-transplant recurrent FSGS and that this may be mediated by nephrin phosphorylation. Larger studies including other ethnicities are required to confirm this finding. Copyright © 2023 International Society of Nephrology. All rights reserved.

Citation

Yoko Shirai, Kenichiro Miura, Kiyonobu Ishizuka, Taro Ando, Shoichiro Kanda, Junya Hashimoto, Yuko Hamasaki, Kiyohiko Hotta, Naoko Ito, Kazuho Honda, Kenji Tanabe, Tomoko Takano, Motoshi Hattori. A multi-institutional study found a possible role of anti-nephrin antibodies in post-transplant focal segmental glomerulosclerosis recurrence. Kidney international. 2024 Mar;105(3):608-617