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Abstract: SA-PO376

Predicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome by Cytokine Profiling

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Agrawal, Shipra, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio, United States
  • Colucci, Manuela, Bambino Gesù Children's Hospital - IRCCS, Rome, Italy
  • Nateri, Jyotsna, Nationwide Childrens Hospital , Columbus, Ohio, United States
  • Hall, Mark W., Nationwide Children''s Hospital, Columbus, Ohio, United States
  • Vivarelli, Marina, Bambino Gesu Children Hospital and Research Center IRCCS, Rome, Italy
  • Smoyer, William E., Nationwide Children's Hospital, Columbus, Ohio, United States
Background

Steroids (glucocorticoids, GC) are the cornerstone of therapy for nephrotic syndrome (NS). However, they only induce remission of NS in ~50% of adults and ~80% of children. Unfortunately, there are no validated biomarkers able to predict steroid response in NS. Several clinical and experimental observations suggest that reversible immune dysregulation is a key feature of idiopathic NS. This study aims to identify early prognostic immunological biomarkers and molecular pathways associated with steroid resistance in NS pediatric patients.

Methods

Paired plasma samples were collected from 26 steroid-sensitive NS (SSNS) and 13 steroid-resistant NS (SRNS) patients, obtained both at initial disease presentation and after ~7 weeks of GC therapy, when SSNS vs SRNS was clinically determined. The cytokine profiling was performed using a 27 cytokine panel on a Luminex® Technology platform using a bead-based fluorescence assay. Data were compared using the nonparametric Wilcoxon signed-rank test and the Mann Whitney U test (statistically significant differences at p<0.05).

Results

In comparison to SSNS, SRNS patients at presentation showed higher plasma levels of IL-1β, IL-6, IL-8, TNF-α, IFN-γ, IL-7, and MIP-1α, and reduced levels of IL-1Ra, IL-2, IL-9, MIP-1β. GC treatment of SSNS patients induced significant reductions in all of the elevated cytokine levels above (IL-6 undetectable at presentation in most SSNS patients). Of note, circulating cytokine levels appear not be influenced by differences in proteinuria, as we found reduced levels in SSNS patients in remission. In contrast, GC therapy in SRNS patients failed to induce remission or to significantly reduce the above plasma cytokine levels (except for TNF-α).

Conclusion

These studies suggest that an increase in a panel of plasma pro-inflammatory cytokines, produced primarily by monocytes/macrophages and Th1 cells, may be able to predict steroid resistance in NS prior to GC treatment. In addition, steroid-resistance is also associated with persistence elevated levels of pro-inflammatory cytokines, suggesting a potential pathogenic role for these circulating factors in SRNS.