Punctate IgG staining particles localize in the budding ballooning clusters of reactive foot processes in minimal change disease

ABSTRACT

The etiology of minimal change disease (MCD) remains a mystery as the only characteristic findings are the diffuse effacement of foot processes seen on electron microscopy (EM). Punctate IgG staining found floating outside glomerular capillary loops in MCD cases was recently identified as autoimmune antibodies against nephrin of podocytes. We hypothesized that the punctate IgG staining is located on budding ballooning clusters (BBC) of reactive foot processes in Bowman’s space found on EM. We identified seven patients with MCD cases showing IgG staining that were subsequently evaluated for BBC on EM. We concurrently examined 12 negative controls, either unremarkable cases or tubulointerstitial diseases, by EM. Immunogold labeling was performed to confirm the presence of IgG and determine localization. In seven MCD cases, there were positive punctate IgG staining particles outside of the glomerular basement membranes (GBM) along with concurrent punctate staining for C3, kappa, and lambda. By EM, all seven (100%) MCD cases revealed BBC that was characterized by ballooning foot processes ranging from 1 to 6 µm and was either budding or detached from the GBM in 3–7 clusters; no electron-dense materials were seen in BBC. BBC was also seen in only 1 of 12 (8%) negative controls. Immunogold labeling identified IgG particles within BBC of MCD by EM, but not in the negative control. Our data suggest that BBC are EM structures of reactive foot processes that are most likely correlated with punctate IgG staining seen in cases of MCD, supported by immunogold labeling for IgG.

KEYWORDS:

• And immunogold label
• budding ballooning cluster
• minimal change disease
• primary focal segmental glomerulosclerosis
• punctate IgG

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Author contributions

Conception and design, analysis and interpretation of the data: PLZ, GAH; the drafting of the paper, revising it critically for intellectual content: PLZ, VDM, BDM, YAO, GAH; the final approval of the version to be published: PLZ, VDM, BDM, YAO, HDK, WL, HDK, GAH; all authors agree to be accountable for all aspects of the work.

Ethical approval

This retrospective study was approved by Institutional Board Review, Corewell Health East, Royal Oak, MI.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.