Minimal change disease (MCD) and primary (idiopathic) focal segmental glomerulosclerosis (1FSGS), referred to collectively as “primary podocytopathies”, are major causes of nephrotic syndrome in children and adults, and are thought to be due to direct podocyte damage visible only at the electron microscopic level. Lupus podocytopathy (LP) is a newly recognized entity that involves severe podocyte injury in the setting of systemic lupus erythematosus, in the complete absence of peripheral capillary wall immune deposits. All of these pathologic diagnoses hinge on the ultrastructural finding of severe podocyte injury and foot process effacement. In addition to these ultrastructural changes, we have observed the presence of fine granular anti-IgG antibody immunoreactivity on podocyte cell bodies in kidney biopsies of patients with MCD, LP, and some patients with the tip lesion variant and NOS variants of 1FSGS. To validate this finding, we compared antibody staining from primary podocytopathy biopsies with those in biopsies from patients with other disease states, including lesions associated with severe podocyte injury in the absence of immune deposits: secondary (adaptive) focal segmental glomerulosclerosis, thin basement membrane disease, diabetic nephropathy, and renal amyloidosis. We found that a fine granular pattern of anti-IgG immunoreactivity on podocyte cell bodies is a specific morphologic feature of the primary podocytopathies, including virtually all cases of MCD that we encountered, some instances of tip lesion variant and NOS variant of 1FSGS, and one cases of LP. The antigen targeted by the anti-IgG immunostaining in these biopsies exhibited one of several oligoclonal IgG heavy chain subtype plus light chain profiles. Ultra-high resolution microscopy revealed fine linear anti-IgG staining along filtration slit diaphragms, suggesting that IgG deposition may potentially be targeting a filtration slit-associated antigen such as podocin. Our findings suggest the possibility of a direct antibody-mediated mechanism of podocyte injury in the primary podocytopathies, one that potentially targets podocyte-specific protein structures, and which may provide a specific and more rapid diagnostic marker for this group of diseases. The findings also suggest an etiologic relationship between MCD and some instances of 1FSGS.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/31223 |
| Date | 11 July 2018 |
| Creators | Chen, Junbo |
| Contributors | Henderson, Joel M., Andry, Christopher D. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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