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Fibrillary glomerulonephritis (FGN) is a relative rare disease accounting for up to 1% of all glomerulonephritis. Monotypic variant is rare subtype of FGN, representing less than 10%. It may represent a diagnostic challenge due to its resemblance to other glomerular pathologies, both clinically and histopathologically. Before a specific immunohistochemical stain of DNAJB9 was discovered, histopathological diagnosis was made based on the presence of typical fibrillar deposits.
Aims: 1) To evaluate, whether light microscopy, immunofluoresence and electron microscopy are accurate to diagnose fibrillary glomerulonephritis without immunohistochemical stain of DNAJB9. 2) To determine the incidence and immunofluorescence types of monotypic FGN. 3) To analyze atypical histopathological patterns of FGN.
This was a retrospective analysis conducted on renal biopsy samples from patients who underwent renal biopsy between 2001-2023 in three center in Czech Republic. All samples were evaluated at the Department of clinical and transplant pathology, Institute for clinical and experimental medicine. In first step, the diagnosis was made by immunohistochemistry, light microscopy and electron microscopy. Second step included reevaluation of all samples using immunohistochemical stain of DNAJB9 and IgG subclasses in clinical correlation. All FGN were diagnosed and then reclassified by a specialized nepropathologist.
A total of 22 patients (12 men, 10 women) with median age of disease presentation 55 years (range 33-75) were included. Five patients (22,7%; 5/22) with previous diagnose of FGN were excluded, while DNAJB9 immunohistochemistry was negative and clinical findings indicated other diseases. Strong deposits of immunoglobulin G (IgG) was positive in all patients (100%) in mezangium and along the glomerular basement membrane. Three cases (17,6%; 3/17) were classified as monotypic FGN (2x lambda restricted, 1x kappa restricted). One other patient showed light chain restriction (kappa positive), nevertheless IgG1 and IgG4 subclasses were positive. Severe crescentic glomerulonephritis affecting more than 75% of vital glomeruli was found in 2 patients (11,7%) both presented with nephrotic range proteinuria.
Immunohistochemical stain of DNAJB9 should be performed in cases with undetermined GN with immunofluorescence IgG positivity and fibrillary deposits. DNAJB9 is superior to electron microscopy to confirm or exclude FGN. Monotypic FGN seems to be more common than previously reported. The most common monotypic variant is IgG1 lambda.
Supported by the Charles University Research program „Cooperatio" - 207034 Internal disciplines.
Supported by Ministry of Health, Czech Republic – conceptual development of research organization 00064165, General University Hospital in Prague.