TY - JOUR
T1 - Diagnostic Approach to Glomerulonephritis With Fibrillar IgG Deposits and Light Chain Restriction
AU - Kudose, Satoru
AU - Canetta, Pietro
AU - Andeen, Nicole K.
AU - Stokes, M. Barry
AU - Batal, Ibrahim
AU - Markowitz, Glen S.
AU - D'Agati, Vivette D.
AU - Santoriello, Dominick
N1 - Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/4
Y1 - 2021/4
N2 - Introduction: The pathologic approach to glomerulonephritis (GN) with fibrillar IgG deposits and light chain restriction remains a diagnostic challenge. Method: All GN with fibrillar deposits of IgG and apparent light chain restriction on standard immunofluorescence on frozen tissue (IF-F) accessioned at the Columbia Renal Pathology Laboratory from 2012 to 2019 were identified. Additional studies including staining for Congo red, DNAJB9, IgG subtypes, and immunofluorescence on pronase-digested paraffin sections (IF-P) were performed. Result: Based on the results, biopsy samples were reclassified as polytypic DNAJB9-positive fibrillary glomerulonephritis (pFGN, n = 14), monotypic DNAJB9-positive FGN (mFGN, n = 7), GN with polytypic DNAJB9-negative fibrillar IgG deposits (n = 2), and GN with monotypic DNAJB9-negative fibrillar IgG deposits (n = 6). Among DNAJB9-positive FGN samples, IgG subtype staining was able to exclude monotypic deposits by demonstrating reactivity for ≥2 IgG subtypes (usually IgG1 and IgG4) in 67% (14 of 21), including 9 that would have been misclassified as monotypic by IF-F and IF-P alone. Monotypic DNAJB9-positive fibrillary glomerulonephritis (FGN) was not associated with monoclonal gammopathy in 5 of 6 patients. GN with monotypic DNAJB9-negative fibrillar IgG deposits exhibited focal parallel fibril alignment and frequent association with chronic lymphocytic leukemia, but lacked the diagnostic microtubules of immunotactoid GN. Conclusion: A systematic diagnostic approach with ancillary techniques is essential for proper classification and assignment of monoclonal gammopathy of renal significance status in cases of GN with fibrillary IgG deposits and light chain restriction by IF-F.
AB - Introduction: The pathologic approach to glomerulonephritis (GN) with fibrillar IgG deposits and light chain restriction remains a diagnostic challenge. Method: All GN with fibrillar deposits of IgG and apparent light chain restriction on standard immunofluorescence on frozen tissue (IF-F) accessioned at the Columbia Renal Pathology Laboratory from 2012 to 2019 were identified. Additional studies including staining for Congo red, DNAJB9, IgG subtypes, and immunofluorescence on pronase-digested paraffin sections (IF-P) were performed. Result: Based on the results, biopsy samples were reclassified as polytypic DNAJB9-positive fibrillary glomerulonephritis (pFGN, n = 14), monotypic DNAJB9-positive FGN (mFGN, n = 7), GN with polytypic DNAJB9-negative fibrillar IgG deposits (n = 2), and GN with monotypic DNAJB9-negative fibrillar IgG deposits (n = 6). Among DNAJB9-positive FGN samples, IgG subtype staining was able to exclude monotypic deposits by demonstrating reactivity for ≥2 IgG subtypes (usually IgG1 and IgG4) in 67% (14 of 21), including 9 that would have been misclassified as monotypic by IF-F and IF-P alone. Monotypic DNAJB9-positive fibrillary glomerulonephritis (FGN) was not associated with monoclonal gammopathy in 5 of 6 patients. GN with monotypic DNAJB9-negative fibrillar IgG deposits exhibited focal parallel fibril alignment and frequent association with chronic lymphocytic leukemia, but lacked the diagnostic microtubules of immunotactoid GN. Conclusion: A systematic diagnostic approach with ancillary techniques is essential for proper classification and assignment of monoclonal gammopathy of renal significance status in cases of GN with fibrillary IgG deposits and light chain restriction by IF-F.
KW - fibrillary
KW - fibrillary glomerulonephritis
KW - immunotactoid glomerulonephritis
KW - monotypic
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U2 - 10.1016/j.ekir.2021.01.001
DO - 10.1016/j.ekir.2021.01.001
M3 - Article
AN - SCOPUS:85101229221
SN - 2468-0249
VL - 6
SP - 936
EP - 945
JO - Kidney International Reports
JF - Kidney International Reports
IS - 4
ER -