Recurrence of DNAJB9-Positive Fibrillary Glomerulonephritis After Kidney Transplantation: A Case Series

Ters, Mireille El; Bobart, Shane A.; Cornell, Lynn D.; Leung, Nelson; Bentall, Andrew; Sethi, Sanjeev; Fidler, Mary E.; Grande, Joseph P.; Hernandez, Loren Herrera; Cosio, Fernando G.; Zand, Ladan; Amer, Hatem; Fervenza, Fernando C.; Nasr, Samih H.; Alexander, Mariam P.

doi:10.1053/j.ajkd.2020.01.018

Cited by 16 publications

(28 citation statements)

References 21 publications

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“…6,18 This hypothesis is supported by the fact that DNAJB9 is overabundant in FGN glomeruli, 5,50 and is detected first in the cases of recurrent FGN post kidney transplantation (despite the absence of IgG staining on IF). 53 This suggests that DNAJB9 deposits precede the IgG deposition suggesting that the most likely initial step in the pathogenesis of the disease is the deposition of DNAJB9 in the kidney. 53 However, so far no auto-antibodies against DNAJB9 have been identified.…”

Section: Discovery Of Dnajb9 In Fgnmentioning

confidence: 99%

“…53 This suggests that DNAJB9 deposits precede the IgG deposition suggesting that the most likely initial step in the pathogenesis of the disease is the deposition of DNAJB9 in the kidney. 53 However, so far no auto-antibodies against DNAJB9 have been identified. 21 In addition, the DNAJB9 protein that is found in FGN is intact without evidence of truncation and thus far no genetic alteration in DNAJB9 gene has been identified among FGN patients.…”

Section: Discovery Of Dnajb9 In Fgnmentioning

confidence: 99%

“…It is unlikely that the source is the kidney itself, as the disease can recur post transplantation. 7,53,54 In addition, there is no evidence of enrichment of other components of ER stress in the glomeruli. 5 Moreover, DNAJB9 is not transcriptionally upregulated in the kidneys of FGN patients.…”

Section: Discovery Of Dnajb9 In Fgnmentioning

confidence: 99%

“…In addition, the finding of DNAJB9 preceding IgG deposition in recurrent FGN post kidney transplantation argues against DNAJB9 secondarily binding to IgG as one would have expected to see IgG deposits either first or simultaneously with DNAJB9 deposition. 53 Serum study of DNAJB9 Serum DNAJB9 level has been studied in FGN in light of the discovery of DNAJB9 in kidney biopsies. Serum levels of DNAJB9 can be measured by immunoprecipitation-linked multiple reaction monitor assay.…”

Section: Discovery Of Dnajb9 In Fgnmentioning

confidence: 99%

“…7,54 However, our recent study using DNAJB9 as a diagnostic tool demonstrated that the rate of recurrence in allograft is 21%. 53 FGN tends to recur late and most patients have recurrence after 5 years. 53 The earliest recurrence was reported at 2 years post-transplant.…”

Section: Recurrence Post Kidney Transplantationmentioning

confidence: 99%

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Fibrillary Glomerulonephritis and DnaJ Homolog Subfamily B Member 9 (DNAJB9)

2020

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Fibrillary GN (FGN) is a rare glomerular disease that is diagnosed based on the presence of fibrils in glomeruli. The fibrils are typically noncongophilic, randomly oriented, and measure 12–24 nm. Traditionally, electron microscopy (EM) has been an important tool to aid in the diagnosis of FGN by identifying the fibrils and to distinguish it from other entities that could mimic FGN. However, recently DnaJ homolog subfamily B member 9 (DNAJB9) has emerged as both a specific and sensitive biomarker in patients with FGN. It allows prompt diagnosis and alleviates reliance on EM. DNAJB9 is a cochaperone of heat shock protein 70 and is involved in endoplasmic reticulum protein-folding pathways. But its role in the pathogenesis of FGN remains elusive. DNAJB9 may act as a putative antigen or alternatively it may secondarily bind to misfolded IgG in the glomeruli. These hypotheses need future studies to elucidate the role of DNAJB9 in the pathogenesis of FGN. The treatment regimen for FGN has been limited due to paucity of studies. Most patients receive combination immunosuppressive regimens. Rituximab has been studied the most in FGN and it may delay disease progression. Prognosis of FGN remains poor and 50% require dialysis within 2 years of diagnosis. Despite its poor prognosis in native kidneys, the rate of recurrence post-transplantation is low (20%) and patient as well as allograft outcomes are similar to patients without FGN.

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