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Glomerular Outgrowth as an Ex Vivo Assay to Analyze Pathways Involved in Parietal Epithelial Cell Activation
Published on: August 19, 2020
Subepithelial deposits with microspherular structures in membranous glomerulonephritis
Hae Yoon Grace Choung1, Jerome Jean-Gilles1, Bruce Goldman1
1Department of Pathology and Laboratory Medicine, Division of Renal Pathology and Electron Microscopy, University of Rochester Medical Center, Rochester, NY, USA.
Abstract:
Rare cases of membranous glomerulopathy (MGN) with subepithelial deposits consisting of microspherular structures identified by electron microscopy have been described in the literature as either MGN with spherules or podocyte infolding glomerulopathy (PIG). The paucity of available studies shows a strong association with underlying autoimmune disease. To further understand the significance of subepithelial microspherular deposits, we retrospectively identified native kidney biopsies from 10 patients diagnosed as MGN with subepithelial microspherular structures identified by ultrastructural examination at the University of Rochester Medical Center (URMC) during an 11-year period. The majority were Caucasian (80%) with a mean age of 51.3 (±12.9) years. 50% had an autoimmune disorder, of which 80% were SLE. Two SLE cases had concomitant rheumatoid arthritis and Sjogren's syndrome. One additional case had antiphospholipid syndrome and showed lupus-like features on biopsy. 40% were idiopathic and negative for PLA2R, NELL1, and THSD7A. MGN with subepithelial microspherular structures is frequently associated with an underlying autoimmune disease. The majority are negative for markers of primary MGN (PLA2R, THSD7A, and NELL1) and show features suggestive of secondary MGN.
Insights
Membranous glomerulopathy (MGN) with subepithelial microspherular structures often indicates an underlying autoimmune disease, particularly lupus. Many cases lack primary MGN markers, suggesting secondary causes.
Area of Science:
- Nephrology
- Pathology
- Immunology
Background:
- Membranous glomerulopathy (MGN) can present with unique subepithelial microspherular structures.
- These structures have been termed MGN with spherules or podocyte infolding glomerulopathy (PIG).
- Previous studies suggest a link to autoimmune conditions, but further investigation is needed.
Purpose of the Study:
- To investigate the clinical significance and underlying causes of MGN with subepithelial microspherular structures.
- To determine the association with autoimmune diseases and common primary MGN markers.
Main Methods:
- Retrospective analysis of 10 native kidney biopsies with identified subepithelial microspherular structures.
- Review of patient demographics, clinical history, and autoimmune markers.
- Immunohistochemical staining for PLA2R, NELL1, and THSD7A.
Main Results:
- The majority of patients were Caucasian (80%) with a mean age of 51.3 years.
- 50% of cases were associated with autoimmune disorders, predominantly Systemic Lupus Erythematosus (SLE) (80% of autoimmune cases).
- 40% of cases were idiopathic and negative for PLA2R, NELL1, and THSD7A, suggesting secondary MGN.
Conclusions:
- MGN with subepithelial microspherular structures is frequently associated with underlying autoimmune diseases.
- The frequent absence of primary MGN markers supports a diagnosis of secondary MGN in these cases.
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