Letter Regarding “Fibrillary Glomerulonephritis Is Associated With HLA-DR7 and HLA-B35 Antigens”

Ters, Mireille El; Gandhi, Manish J.; Moyer, Ann M.; Nasr, Samih H.; Alexander, Mariam P.

doi:10.1016/j.ekir.2020.08.015

Cited by 3 publications

(4 citation statements)

References 4 publications

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“…Unlike our study, HLA-B35 was not significantly associated with FGN in the Mayo Clinic cohort, 2 raising uncertainty about the significance of HLA-B35 association with FGN. HLA antigens have associations with race and infectious and autoimmune diseases, that may confound analyses of small cohorts.…”

contrasting

confidence: 99%

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Andeen

Smith

Vasilescu

et al. 2020

Kidney International Reports

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contrasting

confidence: 99%

“… 1 We are pleased that El Ters et al. 2 have observed a similar association between HLA-DR7 and FGN in their cohort of 16 patients with native kidney failure due to FGN or donor-derived FGN. Together, these findings support a genetic component to this rare glomerulonephritis.…”

mentioning

confidence: 72%

The Authors Reply

Andeen

Smith

Vasilescu

et al. 2020

Kidney International Reports

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“…We identified HLA-DR7 (in 50% of FGN patients) and HLA-B35 as significantly associated with FGN [23 ▪ ]. The association between HLA-DR7, but not B35, was confirmed in a separate cohort by El Ters et al [24 ▪ ]. HLA-DR7 has also been described as a risk factor for steroid-sensitive nephrotic syndrome [25].…”

Section: Clinical and Genetic Associationssupporting

confidence: 59%

DNA J homolog subfamily B member 9 and other advances in fibrillary glomerulonephritis

Andeen

Avasare²

2021

Current Opinion in Nephrology &Amp; Hypertension

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Purpose of review Fibrillary glomerulonephritis (FGN) involves ∼1% of native kidney biopsies and is characterized by glomerular deposition of fibrils larger than amyloid (12–24 nm diameter) composed of polyclonal immunoglobulin G (IgG). The recent discovery of DNA J homolog subfamily B member 9 (DNAJB9) in FGN glomerular deposits has contributed a specific and sensitive biomarker, informing morphologic classification and pathogenesis. This review will consider contemporary FGN incidence and genetics, pathogenesis, (lack of) paraprotein association, variants, treatment, and transplantation. Recent findings DNAJB9 tissue assays have enabled the identification of morphologic variants and improved classification of fibrillary-like glomerular diseases. Together with paraffin immunofluorescence and IgG subclass studies, these have established that FGN is only rarely monoclonal and these patients usually do not have an monoclonal gammopathy. The discovery of DNAJB9 opens new avenues of investigation into FGN pathogenesis, especially those of the unfolded protein response. Treatment for FGN remains empiric, with some encouraging data on rituximab-based therapy. Transplantation is a good option for patients progressing to end-stage kidney disease. Summary Advances building on the discovery of DNAJB9 in FGN should lead to long-term evolution in targeted treatment and outcome of this glomerular disease.

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“…Human leukocyte antigens (HLAs) are inheritable modulators of disease. HLA-DR7 was identified in 50% of FGN patients (compared with a prevalence of ∼20-25% in deceased donor controls and the US population) who had progressed to end-stage kidney disease (ESKD) and was significantly associated with FGN on multivariable analyses, in two separate cohorts [27,28]. HLA-DR7 has also been described as a risk factor for steroidsensitive nephrotic syndrome [29].…”

Section: Genetic Associations Of Fgnmentioning

confidence: 99%

Fibrillary Glomerulonephritis, DNAJB9, and the Unfolded Protein Response

et al. 2022

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Background: Fibrillary glomerulonephritis (FGN) is found in approximately 1% of native kidney biopsies and was traditionally defined by glomerular deposition of fibrils larger than amyloid (12-24nm diameter) composed of polyclonal IgG. Recent identification of DNAJB9 as a sensitive and specific marker of FGN has revolutionized FGN diagnosis and opened new avenues to studying FGN pathogenesis. In this review, we synthesize recent literature to provide an updated appraisal of the clinical and pathologic features of FGN, discuss diagnostic challenges and pitfalls, and propose molecular models of disease in light of DNAJB9. Summary: DNAJB9 tissue assays, paraffin immunofluorescence studies, and IgG subclass testing demonstrate that FGN is distinct from other glomerular diseases with organized deposits and highlight FGN morphologic variants. Additionally, these newer techniques show that FGN is only rarely monoclonal, and patients with monoclonal FGN usually do not have a monoclonal gammopathy. DNAJB9 mutation does not appear to affect the genetic architecture of FGN, however, the accumulation of DNAJB9 in FGN deposits suggests that disease is driven, at least in part, by proteins involved in the unfolded protein response. Treatments for FGN remains empiric, with some encouraging data suggesting that rituximab-based therapy is effective and that transplantation is a good option for patients progressing to ESKD. Key Messages: DNAJB9 aids in distinguishing FGN from other glomerular diseases with organized deposits. Further investigations into the role of DNAJB9 in FGN pathogenesis are necessary to better understand disease initiation and progression, and to ultimately develop targeted therapies.

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Letter Regarding “Fibrillary Glomerulonephritis Is Associated With HLA-DR7 and HLA-B35 Antigens”

Cited by 3 publications

References 4 publications

The Authors Reply

The Authors Reply

DNA J homolog subfamily B member 9 and other advances in fibrillary glomerulonephritis

Fibrillary Glomerulonephritis, DNAJB9, and the Unfolded Protein Response

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