Abstract: SA-PO674
The Role of TNFα/TNF Receptor 2 Pathway Activation in the Modulation of Childhood Nephrotic Syndrome
Session Information
- Pediatric Glomerular Disease
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Pediatric Nephrology
- 1700 Pediatric Nephrology
Authors
- Fisher, Dor, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
- Herman-Edelstein, Michal, Felsenstein Medical Research Center and Department of Nephrology, Rabin Medical Center, Petah Tikva, Israel
- Davidovits, Miriam, Schneider Children's Medical Center of Israel, Petah Tikva, Israel
Background
Primary Nephrotic Syndrome (NS) is considered T cell pathology; however, the pathogenesis still remains poorly defined. There is increasing evidence pointing to the important role of tumor necrosis factor-alpha (TNFα), a key inflammatory mediator, in pediatric nephrotic syndrome. We recently showed that elevated serum TNFα levels were associated with worse prognosis and lack of response to corticosteroids in children with NS. TNFα exerts its biological effect via interaction with two main cell surface receptors: tumor necrosis factor receptor 1 (TNFR1), and tumor necrosis factor receptor 2 (TNFR2), that contribute differently to glomerular inflammation. The aim of the present study was to investigate the expression and the role of different TNFα receptors and TNFα signaling pathways in kidney biopsies of children with steroid responsive and steroid resistant nephrotic syndrome.
Methods
TNFα and TNFα receptors expression were studied by immunofluorescence staining and RNA isolation from formalin-fixed, paraffin-embedded (FFPE) renal biopsies of children with nephrotic syndrome who were treated in our department (n=40) versus normal kidneys (n=12).
Results
TNFα and TNFR2 expression was significantly elevated in both children with steroid sensitive and resistant nephrotic syndrome, versus control group. Furthermore, TNF protein and mRNA abundancey were increased in steroid resistant nephrotic syndrome kidneys compared with steroid sensitive nephrotic syndrome kidneys. TNFα and TNFR2 but not TNFR1 expression positively correlated with steroid resistance and disease progression. In addition, TNFα signaling proteins (TRAF1, TRAF2, CCL2, CCL4, CCL10, CCL11, MMP2, MMP9, TIMP1, ADAM17, IL1b, IL6 and others) were also increased in children with NS and predicted prognosis and steroid responsivness.
Conclusion
As yet there is little information regarding the pathogenesis and optimal treatment of pediatric nephrotic syndrome, our results may indicate that TNFα pathway has a role in the pathogenesis of steroid resistant nephrotic syndrome, and may serve as a target for future therapy.