Abstract: SA-OR75
Immunomodulatory Effects of Levamisole in Children with Idiopathic Nephrotic Syndrome
Session Information
- Pediatric Nephrology: Insights and Innovations
October 26, 2024 | Location: Room 23, Convention Center
Abstract Time: 04:50 PM - 05:00 PM
Category: Pediatric Nephrology
- 1900 Pediatric Nephrology
Authors
- Bouts, Antonia, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, NH, Netherlands
- Veltkamp, Floor, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, NH, Netherlands
- Khan, Gerarda H., Amsterdam UMC Locatie AMC, Amsterdam, Noord-Holland, Netherlands
Group or Team Name
- LEARNS Consortium.
Background
This study aimed to systematically investigate the effects of Levamisole (LMS) on the human immune system, including its impact on isolated human immune cells in vitro. The objectives were to elucidate the immunological mechanisms underlying idiopathic nephrotic syndrome (INS) in children, assess the immunomodulatory effects of LMS, and investigate its potential therapeutic implications in INS management
Methods
Blood samples were collected from INS pediatric patients and age-matched healthy controls (HC) for flow cytometry and immunoplexing analysis. Additionally, whole blood samples from INS patients treated with LMS or placebo were stimulated with lipopolysaccharide (LPS) or anti-CD3/anti-CD28, and cytokine production was measured.
Results
Compared to HC, INS patients exhibited elevated levels of circulating T-cells, particularly CD8+ T-cells, and an increased presence of plasmablasts. Moreover, INS patients demonstrated heightened IgM production and reduced IgG levels at diagnosis, suggesting early activation of the humoral immune response. LMS-treated patients showed decreased B-cell counts and altered cytokine profiles, with enhanced production of TNF-α, IFN-γ, and IL-2 upon stimulation, and reduced levels of IL-13 compared to placebo-treated patients. Earlier work from our group has shown that LMS suppresses the proliferation and activation of both CD4+ and CD8+ T-cells by modulating gene expression associated with cell cycle progression and p53 activation [1]. Additionally, LMS treatment decreases B-cell proliferation, Ig production, and metabolism, while inducing upregulation of genes involved in plasmablast differentiation.
Conclusion
These findings highlight the immunomodulatory effects of LMS on the human immune response, shedding light on its potential therapeutic role in INS management in children. LMS appears to suppress immune cell proliferation, alter gene expression profiles, and induce DNA damage, suggesting its capacity as an immunosuppressive agent. Further research is needed to fully elucidate the therapeutic implications of LMS in immune-mediated disorders and its underlying mechanisms of action.
[1]. Khan et al. European Journal of Immunology 2023 Nov;53(11):e2350562.
Funding
- Private Foundation Support