ArticleItalian journal of pediatrics2026
Serum IL-38 and the rs7599662 polymorphism: novel biomarkers for pediatric idiopathic nephrotic syndrome.
Article in Italian journal of pediatrics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundIdiopathic nephrotic syndrome (INS) is the most common chronic glomerular disorder in children and is characterized by a variable response to corticosteroid therapy. Interleukin-38 (IL-38), an anti-inflammatory cytokine, and its gene polymorphisms may influence disease susceptibility and treatment outcomes. This study investigated the associations between serum IL-38 levels, the rs7599662 gene polymorphism, and disease presence in pediatric INS patients.
methodsThis case‒control study included 88 pediatric INS patients and 74 age- and sex-matched healthy controls. Patients were categorized as steroid sensitive (50%), steroid dependent (25%), or steroid resistant (25%). Serum IL-38 was measured by ELISA, and rs7599662 (C/T) genotyping was performed via real-time PCR. Statistical analyses included nonparametric tests, chi-square tests, Spearman correlation, and receiver operating characteristic (ROC) curve analysis.
resultsSerum IL-38 levels were significantly lower in patients than in controls (17.9 ± 11.4 vs. 38.8 ± 35.6 ng/L, p < 0.001). IL-38 was negatively correlated with age (r = -0.28, p = 0.01), systolic blood pressure (r = -0.28, p = 0.01), and urinary protein (r = -0.38, p = 0.001). ROC analysis revealed that IL-38 had moderate diagnostic performance (AUC = 0.687, p < 0.001), with 73.7% sensitivity and 63.8% specificity at a cutoff of 18.773 ng/L. The CT genotype was significantly more common in patients (p = 0.003), with a protective association observed for the TT genotype under a recessive model (p = 0.002). Serum IL-38 levels did not differ among steroid-sensitive, dependent, or resistant subgroups (p = 0.32).
conclusionThis first report of reduced serum IL-38 and the rs7599662 polymorphism in pediatric INS suggests a role for impaired anti-inflammatory responses in disease pathogenesis. Serum IL-38 shows promise as a diagnostic biomarker and may reflect disease pathophysiology, but does not predict steroid responsiveness. These hypothesis-generating findings require validation in larger, prospective, multicenter studies to establish their clinical utility. The primary value of this work lies in generating testable hypotheses for future confirmatory studies rather than providing definitive mechanistic answers.
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