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Serum from minimal change patients in relapse increases CD80 expression in cultured podocytes
Takuji Ishimoto1, Gabriel Cara-Fuentes, Heiman Wang
1Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado, Denver, CO, USA.
Background:
Minimal change disease (MCD) is the most common cause of nephrotic syndrome in children and is associated with the expression of CD80 in podocytes and the increased excretion of CD80 in urine. We hypothesized that serum from patients with MCD might stimulate CD80 expression in cultured podocytes.
Methods:
Sera and peripheral blood mononuclear cells (PBMCs) were collected from subjects with MCD in relapse and remission and from normal controls. Immortalized human podocytes were incubated with culture media containing patient sera or supernatants from patient and control PBMC cultures. CD80 expression was measured by quantitative PCR and western blot analysis.
Results:
Sera collected from patients with MCD in relapse, but not in remission, significantly increased CD80 expression (mean ± standard deviation: 1.8 ± 0.7 vs. 0.8 ± 0.2; p < 0.004) and CD80 protein secretion by podocytes (p < 0.05 between relapse and normal controls). No such CD80 increase was observed when podocytes were incubated with supernatants of PBMC cultures from patients in relapse.
Conclusions:
Sera from MCD patients in relapse, but not in remission, stimulated CD80 expression in cultured podocytes. Identifying this factor in sera could provide insights into the pathogenesis of this disorder. No role in CD80 expression by podocytes was found for cytokines released by PBMCs.
Insights
Serum from minimal change disease (MCD) patients in relapse, not remission, boosts CD80 expression in podocytes. This finding may reveal new insights into MCD pathogenesis and CD80
Area of Science:
- Nephrology
- Immunology
- Cell Biology
Background:
- Minimal change disease (MCD) is a leading cause of nephrotic syndrome in children.
- MCD is linked to CD80 expression in podocytes and increased urinary CD80 levels.
Purpose of the Study:
- To investigate if serum from MCD patients stimulates CD80 expression in cultured podocytes.
- To explore the role of serum factors in MCD pathogenesis.
Main Methods:
- Collected sera and peripheral blood mononuclear cells (PBMCs) from MCD patients (relapse/remission) and controls.
- Incubated human podocytes with patient sera or PBMC supernatants.
- Quantified CD80 expression using qPCR and western blot.
Main Results:
- MCD patient sera during relapse significantly increased podocyte CD80 expression and secretion.
- No significant increase in CD80 was observed with sera from MCD patients in remission.
- PBMC supernatants from relapsed MCD patients did not affect podocyte CD80 expression.
Conclusions:
- Serum factors in relapsed MCD patients stimulate CD80 expression in podocytes.
- Identifying these serum factors could illuminate MCD pathogenesis.
- Cytokines from PBMCs do not appear to play a direct role in podocyte CD80 upregulation.
