Donald Houghton

School of Medicine, Pathology

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Membranous Glomerulopathy With Spherules: An Uncommon Variant With Obscure Pathogenesis

Jolanta Kowalewska; Kelly D. Smith; Kelly L. Hudkins; Anthony Chang; Agnes B. Fogo; Donald Houghton; Deena Leslie; John Aitchison; Roberto F. Nicosia; Charles E. Alpers (Profiled Author: Donald Houghton)

American Journal of Kidney Diseases. 2006;47(6):983-992.

Background: Occasional case reports of membranous glomerulopathy described unique subepithelial accumulations of an unusual type of immune deposit composed of spherular structures. The identity of such structures as nuclear pores has been suggested, but not established. Methods: We identified a cohort of patients (n = 14, including 1 patient with disease recurrence in an allograft) who presented with nephrotic syndrome and had renal biopsy specimens with light and immunofluorescence microscopic findings characteristic of membranous glomerulopathy. These patients were distinguished by ultrastructural studies that showed glomerular capillary wall accumulations of subepithelial immune deposits composed of uniform spherular structures, while lacking the typical granular electron-dense deposits seen in membranous glomerulopathy. The molecular identity of these spherular structures as nuclear pores was tested by using immunofluorescence microscopy and immunohistochemistry with mouse monoclonal antinuclear pore antibodies (Covance, Princeton, NJ) and anti-Nuclear Pore-O-Linked Glycoprotein (Affinity BioReagents Inc, Golden, CO) antibodies. Results: Measurement of spherular structures by using high-magnification electron microscopy showed an average diameter of 84.5 nm, which correlated well with accepted diameters of nuclear pores (80 to 120 nm). Immunofluorescence microscopy and immunoperoxidase staining with both antibodies showed characteristic beaded staining of nuclear membranes of multiple cell types within normal control kidney, but no staining of immune-type deposits within glomerular basement membranes. Conclusion: These cases form a rare, but distinctive, morphological subclass of membranous glomerulopathy. The antigenic specificity of immune deposits in these cases remains elusive. © 2006 National Kidney Foundation, Inc.

PMID: 16731293    

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