Arhgap24 Downregulation Is Associated with Foot Process Effacement in Minimal Change Disease
Shreeram Akilesh, Joshua Samuel, Joseph Gaut, Sanjay Jain, Andrey Shaw, Helen Liapis. Barnes-Jewish Hospital, St. Louis, MO; Washington University School of Medicine, St. Louis, MO
Background: In vitro studies on glomerular epithelial cells (podocytes) suggest that increased membrane motility may contribute to foot process effacement and proteinuria. Recently, we identified Arhgap24, as a gene that suppresses membrane dynamics of podocytes in vitro. In human and murine kidney, podocytes normally express high levels of Arhgap24 protein, but the protein is susceptible to degradation. Therefore, we hypothesized that Arhgap24 levels would be reduced in proteinuric kidney diseases such as Minimal Change Disease (MCD) where foot process effacement is the key diagnostic feature.
Design: We developed new antibody reagents to stain for Arhgap24 and validated their specificity. Using these antibodies, in a proof of concept study, we stained fresh frozen normal kidney and biopsy material from a 10 year old boy with MCD (proven by electron microscopy). We examined the immunofluorescent staining intensity of Arhgap24 in podocytes in both samples.
Results: 1) Our newly developed antibodies stain Arhgap24 in human podocytes in fresh frozen kidney tissue (Figure 1, left panel).
2) Arhgap24 levels are decreased in a patient with minimal change disease (Figure 1, right panel).
Conclusions: Our cell biological studies predicted that Arhgap24 downregulation would increase podocyte membrane motility in vitro and cause foot process effacement in vivo. Here we show, in a pilot study, that Arhgap24 expression is indeed decreased in a patient with diagnosed MCD, the prototypic kidney disease with foot process effacement. We are currently extending this study to additional patients and will also test the antibody reagents on FFPE kidney tissue. If successful, Arhgap24 downregulation would be a useful IHC marker of MCD when electron microscopy is not available. This study also shows how understanding of the cell biology of cultured podocytes can lead to a useful prediction of biologic behavior in patients.
Category: Kidney (does not include tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 249, Monday Morning