MicroRNA-cytokine interplay and treg dysregulation in pediatric immune thrombocytopenia: implications for disease chronicity

This study aimed to investigate the immune-epigenetic profile of pediatric immune thrombocytopenic purpura (ITP) and its association with disease chronicity. This case–control study included 93 participants: 33 children with newly diagnosed ITP, 28 with chronic ITP (> 12 months), and 32 age- and sex-matched healthy controls. We assessed platelet count, serum transforming growth factor-β (TGF-β), interleukin-10 (IL-10) levels, circulating CD4⁺CD25⁺FoxP3⁺ Treg frequency, and relative expression of miR-106b-5p and miR-146a-5p. ITP patients demonstrated significantly lower platelet counts, Treg frequency, and TGF-β levels, with elevated IL-10 levels compared to controls. miR-106b-5p expression was significantly upregulated in ITP, particularly in chronic cases, and negatively correlated with platelet count, Treg frequency, and TGF-β. Conversely, miR-146a-5p was significantly downregulated and positively correlated with platelet count and Treg frequency. Chronic ITP exhibited more pronounced miRNA dysregulation and Treg depletion. ROC analysis revealed high diagnostic accuracy of both miRNAs for chronic ITP, with miR-146a-5p demonstrating superior sensitivity. Conclusion: This study highlights the interplay between immune dysregulation and epigenetics in ITP. The opposing roles of miR-106b-5p and miR-146a-5p in Treg function and cytokine homeostasis suggest their potential contribution to disease chronicity and their potential as chronicity biomarkers. These findings provide a foundation for future research aimed at improving ITP patient stratification, identifying therapeutic targets, and advancing precision-based interventions. What is Known: • Despite extensive research, the aetiopathogenesis of immune thrombocytopenic purpura (ITP) remains incompletely understood, involving complex interactions between immune dysregulation, cytokine imbalance, and emerging epigenetic factors, such as microRNAs. • This work aimed to investigate the immunological and molecular mechanisms underlying ITP in the pediatric population, focusing on cytokine profiles (TGF-β, IL-10), regulatory T cells (Tregs), and the relative expression of miR-106b-5p and miR-146a-5p, and to assess their value as predictive tools for chronic ITP. What is New: • This study highlights the critical interplay between immune dysregulation and epigenetics in ITP. The opposing roles of miR-106b-5p and miR-146a-5p suggest their involvement in disease chronicity. These miRNAs may serve as non-invasive markers for ITP chronicity and as candidate targets for therapy to restore immune tolerance in ITP. Despite the cross-sectional nature of the current work, it provides a foundation for future research aimed at improving ITP patient stratification, identifying therapeutic targets, and advancing precision-based interventions.