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Any value of podocyte B7-1 as a biomarker in human MCD and FSGS?
Rubina Novelli1, Elena Gagliardini1, Barbara Ruggiero1
1IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, Bergamo, Italy;
Abstract:
Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are the most common causes of nephrotic syndrome in children and in young adults. Relapsing MCD carries the risk of severe complications and prolonged immunosuppression, whereas FSGS remains largely untreatable and urgently needs more effective treatments. Recently, induction of B7-1 (CD80), an immune-related protein expressed by antigen-presenting cells, was observed in podocytes of MCD and FSGS patients, suggesting that B7-1 plays a role in the pathogenesis of these diseases, and hence that abatacept, a B7-1 inhibitor, could be a possible treatment. Since previous studies raised serious concerns regarding the reliability of immunohistochemical assays for B7-1 detection and the efficacy of B7-1 inhibitory treatment, we investigated B7-1 podocyte expression in MCD and FSGS patients. Using different primary antibodies and immunohistochemical assays, no significant upregulation of podocyte B7-1 was detected in patients' biopsies compared with controls. To further confirm our findings, we analyzed mice with adriamycin-induced nephropathy, a model of human FSGS, and mice injected with LPS as additional control. Podocyte B7-1 was not observed in mice injected with adriamycin or LPS either. In conclusion, since B7-1 is not induced in podocyte of MCD and FSGS patients, the antiproteinuric action of abatacept, if confirmed, may not be the result of an effect on podocyte B7-1.
Insights
This study found no evidence of B7-1 protein in the podocytes of patients with minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Therefore, abatacept
Area of Science:
- Nephrology
- Immunology
- Pathology
Background:
- Minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS) are leading causes of nephrotic syndrome in children and young adults.
- FSGS requires more effective treatments, and relapsing MCD can lead to complications.
- B7-1 (CD80) induction in podocytes was proposed as a mechanism in MCD/FSGS, suggesting B7-1 inhibitors like abatacept as potential therapies.
Purpose of the Study:
- To investigate the expression of B7-1 in podocytes of patients with MCD and FSGS.
- To evaluate the reliability of previous findings regarding B7-1 expression and its role in MCD/FSGS pathogenesis.
- To determine if abatacept's potential therapeutic effects in these conditions are mediated through podocyte B7-1.
Main Methods:
- Utilized various primary antibodies and immunohistochemical assays to detect B7-1 expression in kidney biopsies from MCD and FSGS patients.
- Compared B7-1 expression in patient biopsies against control samples.
- Analyzed B7-1 expression in mouse models of FSGS (adriamycin-induced nephropathy) and controls (LPS injection).
Main Results:
- No significant upregulation of B7-1 was detected in the podocytes of MCD and FSGS patients compared to controls.
- Podocyte B7-1 expression was also absent in mice with adriamycin-induced nephropathy and LPS-injected controls.
- Findings challenge the hypothesis that B7-1 induction in podocytes is a key factor in MCD and FSGS.
Conclusions:
- B7-1 is not induced in the podocytes of patients suffering from minimal change disease or focal segmental glomerulosclerosis.
- The antiproteinuric effect of abatacept, if it exists, may not be related to its action on podocyte B7-1.
- Further research is needed to elucidate the mechanisms behind MCD/FSGS and identify effective therapeutic targets.
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