Elsevier

Kidney International

Volume 98, Issue 2, August 2020, Pages 498-504
Kidney International

Clinical Investigation
DNAJB9-positive monotypic fibrillary glomerulonephritis is not associated with monoclonal gammopathy in the vast majority of patients

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The association of fibrillary glomerulonephritis (FGN) with monoclonal gammopathy has been controversial, although monotypic FGN is currently classified as a monoclonal gammopathy of renal significance (MGRS) lesion. To define this lesion, we correlated findings by immunofluorescence on frozen and paraffin tissue, IgG subtype staining and serum protein electrophoresis with immunofixation in patients with monotypic FGN. Immunofluorescence was performed on paraffin sections from 35 cases of DNAJB9-associated FGN that showed apparent light chain restriction of glomerular IgG deposits by standard immunofluorescence on frozen tissue. On paraffin immunofluorescence, 15 cases (14 lambda and one kappa restricted cases on frozen tissue immunofluorescence) showed no light chain restriction, 19 showed similar light chain restriction, and one was negative for both light chains. Seven of the 15 cases with masked polyclonal deposits also had IgG subclass restriction and these cases would have been diagnosed as a form of monoclonal protein-associated glomerulonephritis if paraffin immunofluorescence was not performed. Monotypic FGN (confirmed by paraffin immunofluorescence and IgG subclass restriction) accounted for only one of 151 (0.7%) patients with FGN encountered during the last two years. Only one of 11 of cases had a detectable circulating monoclonal protein on serum protein electrophoresis with immunofixation. We propose that paraffin immunofluorescence is required to make the diagnosis of lambda-restricted monotypic FGN as it unmasked polytypic deposits in over half of patients. When confirmed by paraffin immunofluorescence and IgG subclass staining, DNAJB9-positive monotypic FGN is very rare and is not associated with monoclonal gammopathy in the vast majority of patients. Thus, there is a question whether this lesion should be included in MGRS-related diseases.

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Results

We performed IF-P on 35 cases of FGN that showed apparent light chain restriction on IF-F (which accounted for 9% of our FGN cases, see the Methods section) and correlated the findings by IF-P with IF-F, IgG subtype staining, and serum protein electrophoresis with immunofixation (SPEP/SIF). Data on the clinical characteristics and pathologic findings on light microscopy, immunofluorescence, and electron microscopy for each patient are provided in Table 1, Table 2, Table 3. The mean age at

Discussion

This is the first study to correlate the findings by IF-F, IF-P, IgG subtype staining and SPEP/SIF in the subset of FGN cases that exhibit apparent light chain restriction on routine IF-F. Nine percent of our cases of FGN exhibited light chain restriction on IF-F, in agreement with previous reports.2,3,5, 6, 7 The majority of our cases showed λ restriction in contrast to a recent large multicenter study by Andeen et al.13 in which κ restriction was more frequent. Sixty-three percent of these

Study patients

We retrospectively reviewed the renal pathology archives at Mayo Clinic, Rochester, from January 2011 through October 2019 and identified 35 patients with native kidney FGN in whom the IgG deposits on IF-F showed light chain isotype restriction and in whom staining for λ and κ by IF-P was performed. Fourteen of these cases were accessioned between September 2017 and October 2019 since we started routinely performing IF-P on FGN cases with apparent light chain isotype restriction on IF-F. These

Disclosure

All the authors declared no competing interests.

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