#PathPointer: Membranous-Like Glomerulopathy With Masked IgG Kappa Deposits

PathPointers highlight important everyday teaching points when reviewing kidney histology. These brief and easy-to-read blog posts include real clinical images to demonstrate various biopsy findings.


Most kidney biopsy diagnoses can be made with light, immunofluorescence, and electron microscopy. Paraffin immunofluorescence (IF-P) is performed on pronase-digested paraffin embedded tissue, commonly as a salvage technique when there is inadequate tissue submitted for traditional IF performed on frozen tissue (IF-F). Although less sensitive than IF-F for some diseases, IF-P is extremely useful and required to “unmask” certain immune deposits.  The mechanism by which immune deposits can rarely be “masked,” rendering them undetected by IF-F, is unknown; antigenic epitopes may not be available for binding due to alterations in protein structure, or immune complexes may be altered by transport media, among other possibilities. This case highlights the utility of IF-P to make the correct diagnosis.

A 22-year-old woman presented with 2 weeks of petechial rash, subnephrotic range proteinuria and microscopic hematuria. She had no preceding illness. She had a normal creatinine, urine protein:creatinine ratio of 1.5 mg/mg, positive ANA (1:160), normal C3 and C4 levels, and dysmorphic red cells on urine microscopy; remaining serologic workup was normal/negative.

Kidney biopsy (see figure) revealed glomeruli involved by occasionally large, eosinophilic immune deposits, which were segmentally distributed in mesangial and subepithelial regions of peripheral capillary loops, reminiscent of an unusual membranous nephropathy. Features of prominent inflammatory activity – such as endocapillary hypercellularity, necrosis, or crescents – were not present. IF-F showed moderate glomerular C3 staining (2+) with scant polyclonal IgG (0-trace); other immunoreactants were negative. Electron microscopy showed widespread, variably sized mesangial and subepithelial immune deposits.

Membranous-like glomerulopathy with masked IgG kappa immune deposits with A) membranous-like pattern of injury with irregularly distributed, occasionally large mesangial and subepithelial immune deposits (arrows). B) Subepithelial immune deposits with associated podocyte foot process effacement and C) mesangial immune deposits, on electron microscopy. D) Frozen immunofluorescence demonstrates granular mesangial and capillary wall staining for C3, with E) no significant staining for IgG. F) Paraffin immunofluorescence “unmasks” immune deposits composed of IgG and kappa light chain; lambda light chain was negative.

Based on the C3 dominant deposits, the differential would include C3 glomerulonephritis (C3GN) and post-infectious GN, but neither of these were compatible with the clinical or laboratory findings, and the biopsy lacked the glomerular proliferation and inflammation seen in these conditions.  An unusual or secondary membranous nephropathy may be considered based on subepithelial deposit distribution and the positive ANA, but the subnephrotic presentation and scant IgG staining is atypical for membranous nephropathy. Thus, IF-P was performed, and demonstrated “masked” immune deposits which stained for IgG and kappa light chain (2+), without staining for other antibodies. The overall findings are characteristic of membranous-like glomerulopathy with masked IgG kappa deposits (MGMID).

MGMID is diagnosed in approximately 0.1% of kidney biopsies, usually in women younger than 40. In contrast to membranous nephropathy, only 35% are nephrotic; 30% have elevated creatinine at biopsy, and hematuria is common. Approximately 55% have a positive auto-immune serology, including ANA, but few meet criteria for a defined autoimmune disease. Although the “masked” deposits appear monoclonal, the great majority of patients do not have an identifiable paraprotein or lymphoproliferative disorder.

Proteomic evaluation has revealed that the deposits are specifically enriched for serum amyloid P (SAP), further supporting MGMID as a distinct pathogenic entity and separating it from other membranous nephropathies. The pathogenic role of SAP in disease is unknown, and anti-SAP antibodies have not been identified in patients with MGMID.  Optimal treatment for MGMID is not known, and clinical course is unpredictable; approximately 50% have complete or partial remission, and 11% progress to end stage kidney disease.

– Post prepared by Nicole Andeen, AJKDBlog Contributor

Leave a Reply

%d bloggers like this: