Decoding Immune Dysregulation in Childhood Idiopathic Nephrotic Syndrome: Insights From Lymphocyte Subsets and Urinary Cytokine Analysis
A. K. Anju Ashok, Gautom Kumar Saharia, Amit Kumar Satapathy, Manaswini MangarajBackground
Idiopathic nephrotic syndrome (INS) is a primary kidney disease of childhood involving podocytes where immune dysregulation is thought to play a major role in pathogenesis. The aim of the study was to evaluate peripheral lymphocyte subsets and urinary cytokines in children with INS to understand the immune mechanisms and their association with steroid responsiveness.
Methods
This was a prospective longitudinal observational study of children with INS, conducted at a tertiary care hospital from August 2021 to June 2023. A total of 34 children with INS (17 steroid sensitive [SSNS] and 17 steroid resistant [SRNS]) and 17 healthy controls were enrolled. Flow cytometry analyzed CD3+, CD4+, CD8+, and CD19+ lymphocyte subsets, while ELISA estimated urinary IFN‐γ, IL‐4, and IL‐13 at the onset of disease/relapse and during remission.
Results
Children with INS showed significantly higher counts of CD3+, CD4+, CD8+, and CD19+ cells compared to controls ( p < 0.05) at the time of disease onset. SRNS patients had notably higher counts of all these subsets than SSNS patients. Following steroid therapy, CD19+ and CD3+ counts increased in both groups; however, SRNS patients also showed a persistent increase in CD4+ cells and urinary IFN‐γ and IL‐13, suggesting ongoing immune activation. ROC curve analysis identified CD3+, CD4+, and CD19+ counts with moderate diagnostic performance with AUC values ranging from 0.706 to 0.747.
Conclusion
Significant alterations in T‐ and B‐lymphocyte subset populations indicate immune activation in the pathogenesis of childhood INS. The distinct immunological profiles and poststeroid cytokine increases in SRNS patients indicate persistent local immune activation despite treatment.