Lecture Notes on Multi-Trakulosis Dengue-Phobic Syndrome by Marina Livanovi
Speaker Background
- Marina Livanovi
- Trained in PEDS at the University of Pavia, Italy.
- Research fellowship at Harvard, Children's Hospital in Boston focused on neural reseal function.
- Since 2006, she has been with the Division of Pediatric Podiatry at the University of Pavia, Rome.
- Works in the Department of Sensational Research in Pediatric and Immunomediated Venal diseases.
Introduction
- Gratitude for the invitation to speak at the meeting.
- Shift from monogenic diseases to those with unknown pathophysiology.
Nephrotic Syndrome in Children
Overview
- Idiopathic Nephrotic Syndrome is extremely heterogeneous.
- Patients can be steroid-sensitive or steroid-resistant (10-25% resistant).
- Steroid-resistant patients often respond to second-line immunosuppression (e.g., calcineurin inhibitors).
- Some patients progress to end-stage renal disease (ESRD).
Patient Groups
- Steroid-Sensitive Nephrotic Syndrome:
- Often experiences multiple relapses over decades.
- Some progress to adulthood.
- Multi-Drug Resistant Nephrotic Syndrome:
- Those not responding to steroids or second-line treatment.
- Immune-mediated pathophysiology, often recurring post-transplant.
- Genetic forms do not respond to immunosuppression and lead to ESRD.
- Clinical Scenarios:
- Scenario 1: Primary multi-drug resistant child with late-onset nephrotic syndrome who doesn't respond to treatment.
- Scenario 2: Steroid-sensitive child with multiple relapses and significant morbidity despite treatment.
- Scenario 3: Secondary steroid-resistant nephrotic syndrome - challenges with relapse and treatment.
Pathophysiology and Immune System Role
- Lack of clear understanding of the immune dysregulation causing nephrotic syndrome.
- Genome-wide association studies (GWAS) identified genetic variants, particularly in the HLA locus, related to steroid-sensitive nephrotic syndrome.
- Identified SNPs include those impacting T-cell responses.
Treatment Approaches
- Rituximab:
- Anti-CD20 antibody effective in some patients.
- Can lead to remission and decreased relapses.
- Memory B-cell levels may predict relapse.
- Potential for Other Treatments:
- Mesenchymal stromal cells (MSC) studied for their immunomodulatory properties.
- Innovative approaches such as combining therapies (e.g., anti-CD20 with other immunosuppressants).
Conclusion
- Progress made, but significant challenges remain in treating nephrotic syndrome.
- Need for a better understanding of pathophysiology and tailored treatment approaches.
- Collaborative efforts and innovative studies are crucial for the future.
Q&A Highlights
- Memory B-cells and Treatment:
- Importance of understanding B-cell dynamics in treatment response.
- Antigen-Dependent and Independent Effects:
- Discussion on the role of BAF and antibodies in immune responses.
- Gene Therapy Potential:
- Exciting prospects for targeting podocyte functions, gene therapy advancements, and ongoing studies.
These notes summarize key points from Marina Livanovi's lecture on multi-trakulosis dengue-phobic syndrome, focusing on nephrotic syndrome in children, treatment strategies, and implications for future research.