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

Abstract

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.

Fibrillary Glomerulonephritis: A Great Mimicker of Rapidly Progressive Glomerulonephritis

“…The typical presentation is proteinuria, hematuria, hypertension, and worsening renal function. There are no specific guidelines for the management of FGN, as it lacks randomized clinical trials [ 13 ]. In patients who may have secondary causes of FGN, it should be identified and treated.…”

Fibrillary glomerulonephritis or complement 3 glomerulopathy: a rare case of diffuse necrotising crescentic glomerulonephritis with C3-dominant glomerular deposition and positive DNAJB9

“…This relatively new biomarker, first described in relation to FGN in 2017, has a 98% sensitivity and >99% specificity for FGN 8. DNAJB9 is a member of the heat shock protein family and plays a role in protein folding in the endoplasmic reticulum 12. The exact relationship of DNAJB9 with FGN has yet to be determined, but it has been hypothesised that DNAJB9 may be a precursor fibril protein 8 12.…”

“…DNAJB9 is a member of the heat shock protein family and plays a role in protein folding in the endoplasmic reticulum 12. The exact relationship of DNAJB9 with FGN has yet to be determined, but it has been hypothesised that DNAJB9 may be a precursor fibril protein 8 12. Its utility in the evaluation of GN has several benefits.…”

“…Positive DNAJB9 staining alleviates the prior necessity of obtaining EM to diagnose FGN 8. It serves as a confirmatory marker to distinguish FGN from other fibrillary deposition diseases (eg, amyloid, immunotactoid glomerulopathy, fibronectin glomerulopathy) when fibril appearance (size or orientation) on EM is inconclusive 12. Glomerular staining for fibronectin can be helpful to exclude the diagnosis of fibronectin glomerulopathy.…”

Fibrillary Glomerulonephritis and Monoclonal Gammopathy: Potential Diagnostic Challenges

“…developed DNAJB9 immunohistochemistry (IHC) and found high sensitivity and specificity for FGN ( 21 ). DNAJB9 allows a prompt diagnosis and alleviates reliance on EM ( 25 ). It also helped in making the distinction of FGN from amyloidosis, as some FGN may have Congo red positivity ( 26 ), and from other diagnostically challenging cases due to morphologically early or advanced features, or limited glomeruli for immunofluorescence or EM ( 2 ).…”