Effect Of Histone Deacetylase-2 Expression and Activity on Steroid Responsiveness in Egyptian Children with Nephrotic Syndrome | ||
| Zagazig University Medical Journal | ||
| Articles in Press, Accepted Manuscript, Available Online from 30 October 2025 | ||
| Document Type: Original Article | ||
| DOI: 10.21608/zumj.2025.428323.4226 | ||
| Authors | ||
| Hany Elsayed Ibrahim1; Wafaa Abd.Elatif Emam2; Asmaa Hassan Mohamed Hussein* 3; Asmaa Atef Ibrahim4; Mona Hamed Gehad5 | ||
| 1Professor of Pediatrics, Faculty of Medicine, Zagazig University | ||
| 2Professor of Medical Biochemistry, Faculty of Medicine, Zagazig University | ||
| 3MBBCH, Faculty of Medicine, Zagazig University | ||
| 4Lecturer of Medical Biochemistry, Faculty of Medicine, Zagazig University | ||
| 5Assistant Professor of Pediatrics, Faculty of Medicine, Zagazig University | ||
| Abstract | ||
| Background: Nephrotic syndrome (NS) is a common pediatric glomerular disorder with variable response to corticosteroid therapy. Histone deacetylase-2 (HDAC2) has been implicated in glucocorticoid responsiveness through regulation of inflammatory gene expression. This research aimed to evaluate HDAC2 gene expression and enzymatic activity in Egyptian children with NS and their association with steroid responsiveness. Methods: A prospective case–control study was done enrolling 24 pediatric patients diagnosed with nephrotic syndrome and an equal number of healthy children matched for age and sex. Clinical data, laboratory parameters, HDAC2 gene expression (qRT-PCR), and enzyme activity (ELISA) were evaluated at baseline and after 6 weeks of steroid therapy. Results: HDAC2 gene expression was markedly reduced in NS (p<0.001), with SRNS patients showing significantly lower levels than SSNS (p<0.001), while SSNS and controls did not differ (p=0.15). A cutoff of HDAC2 gene expression≤0.6853 predicted SRNS with 100% sensitivity, 63.2% specificity, and 70.8% accuracy (AUC=0.800, p=0.043). HDAC2 activity was also lower in NS than controls (p<0.001). Pre- treatment levels clearly distinguished SSNS, SRNS, and controls (all p<0.001). Post-treatment, activity increased in SSNS (p=0.041) but decreased in SRNS (p=0.002). A cutoff ≤1.95 of HDAC2 enzyme level predicted SRNS with 100% sensitivity, 94.7% specificity, and 95.8% accuracy (AUC=0.995, p<0.001). Correlation analysis showed that HDAC2 gene expression negatively related with serum cholesterol (r=–0.438, p=0.032). Conclusion: Reduced HDAC2 gene expression and enzymatic activity are strongly associated with steroid resistance in childhood NS. HDAC2 activity, in particular, showed excellent diagnostic performance for predicting steroid responsiveness. | ||
| Keywords | ||
| Histone Deacetylase-2 Expression; Steroid Responsiveness; Children; Nephrotic Syndrome | ||
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