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Case series: CTLA4-IgG1 therapy in minimal change disease and focal segmental glomerulosclerosis
Eduardo H Garin1, Jochen Reiser, Gabriel Cara-Fuentes
1Division of Pediatric Nephrology, Department of Pediatrics, University of Florida, 1600 SW Archer Rd., HD214, Gainesville, FL, 32610, USA, garineh@peds.ufl.edu.
Background:
Minimal Change Disease (MCD) in relapse is associated with increased podocyte CD80 expression and elevated urinary CD80 excretion, whereas focal segmental glomerulosclerosis (FSGS) has mild or absent CD80 podocyte expression and normal urinary CD80 excretion.
Methods:
One patient with MCD, one patient with primary FSGS and three patients with recurrent FSGS after transplantation received CD80 blocking antibodies (abatacept or belatacept). Urinary CD80 and CTLA-4 levels were measured by ELISA. Glomeruli were stained for CD80.
Results:
After abatacept therapy, urinary CD80 became undetectable with a concomitant transient resolution of proteinuria in the MCD patient. In contrast, proteinuria remained unchanged after abatacept or belatacept therapy in the one patient with primary FSGS and in two of the three patients with recurrent FSGS despite the presence of mild CD80 glomerular expression but normal urinary CD80 excretion. The third patient with recurrent FSGS after transplantation had elevated urinary CD80 excretion immediately after surgery which fell spontaneously before the initiation of abatacept therapy; after abatacept therapy, his proteinuria remained unchanged for 5 days despite normal urinary CD80 excretion.
Conclusion:
These observations are consistent with a role of podocyte CD80 in the development of proteinuria in MCD. In contrast, CD80 may not play a role in recurrent FSGS since the urinary CD80 of our three patients with recurrent FSGS was only increased transiently after surgery and normalization of urinary CD80 did not result in resolution of proteinuria.
Insights
CD80 blocking antibodies resolved proteinuria in Minimal Change Disease (MCD) by reducing urinary CD80. However, these antibodies did not improve proteinuria in focal segmental glomerulosclerosis (FSGS) patients, suggesting CD80 is not a key factor in FSGS.
Area of Science:
- Nephrology
- Immunology
- Podocyte Biology
Background:
- Minimal Change Disease (MCD) relapse correlates with increased podocyte CD80 and urinary CD80.
- Focal Segmental Glomerulosclerosis (FSGS) shows minimal or absent podocyte CD80 and normal urinary CD80 excretion.
Purpose of the Study:
- To investigate the therapeutic potential of CD80 blocking antibodies in patients with MCD and FSGS.
- To assess the role of CD80 in the pathogenesis of proteinuria in these glomerular diseases.
Main Methods:
- Treatment of patients with MCD and FSGS using CD80 blocking antibodies (abatacept or belatacept).
- Quantification of urinary CD80 and CTLA-4 levels via ELISA.
- Immunohistochemical staining of glomeruli for CD80 expression.
Main Results:
- Abatacept therapy led to undetectable urinary CD80 and transient proteinuria resolution in the MCD patient.
- Proteinuria remained unchanged in primary and recurrent FSGS patients despite CD80 antibody treatment.
- Elevated urinary CD80 post-surgery in one recurrent FSGS patient normalized spontaneously before treatment.
Conclusions:
- Podocyte CD80 appears to play a role in MCD-related proteinuria.
- CD80 may not be a significant factor in the development or progression of recurrent FSGS.
- Urinary CD80 normalization did not correlate with proteinuria resolution in recurrent FSGS.
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