Aras Part Medical International Press International Journal of Medical Parasitology and Epidemiology Sciences 2766-6492 7 3 2026 09 18 Iron Overload–Linked Immunometabolic Dysregulation and John Cunningham Virus Seropositivity in Children with β-Thalassemia Major and Intermedia 183 191 10.34172/ijmpes.6286 EN Murtadha A. AL-Mudhafar https://orcid.org/0000-0002-1690-6259 Ismael Raheem Al‐Muhana https://orcid.org/0000-0002-9986-599X Hussein Ali Kadhum https://orcid.org/0000-0002-0342-8016 Israa Ketab Alyasiri https://orcid.org/0000-0002-6821-7981 Journal Article 10.34172/ijmpes.6286 2020 03 27 2020 06 22 Introduction: β-Thalassemia is a chronic inherited hemoglobin disorder in which repeated transfusion, ineffective erythropoiesis, iron overload, oxidative stress, and immune imbalance may interact. Ferritin is widely used as a clinical marker of iron burden, although it may also reflect inflammation. John Cunningham virus (JCV) usually remains latent but may become clinically relevant when immune regulation is impaired. Irisin is an emerging myokine involved in metabolic, inflammatory, and oxidative pathways. This study evaluated serum ferritin, interleukin-1 receptor antagonist (IL-1RA), interferon-alpha 2 (IFN-α2), JCV IgG/IgM serology, and human irisin in children with β-thalassemia major or intermedia compared with healthy controls. Methods: A case-control design was used. The study included 59 children with β-thalassemia and 30 healthy controls. Patients were classified as β-thalassemia major or intermedia. Serum ferritin, IL-1RA, IFN-α2, JCV IgG, JCV IgM, and irisin were analyzed. Non-parametric statistics, Fisher’s exact test, and Spearman correlation were used. Results: Ferritin was markedly higher in thalassemia patients than controls [median: 2000 vs. 15 ng/mL; P < 0.0001]. JCV IgM positivity was detected only in thalassemia patients [9/59, 15.3%] and not in controls [0/30; P = 0.0258]. JCV IgG positivity was observed in 13.6% of patients and 6.7% of controls. Patients with JCV IgM positivity had higher ferritin than JCV IgM-negative patients [median: 4000 vs. 1842 ng/mL; P = 0.0101]. IL-1RA, IFN-α2, and irisin showed strong positive correlations in thalassemia patients, especially IL-1RA with irisin [ρ = 0.746, P < 0.0001], IL-1RA with IFN-α2 [ρ = 0.650, P < 0.0001], and IFN-α2 with irisin [ρ = 0.676, P < 0.0001]. β-Thalassemia intermedia showed higher IL-1RA, IFN-α2, and irisin than β-thalassemia major. Conclusion: The findings suggest that pediatric β-thalassemia was associated with severe iron overload, JCV IgM seropositivity, and coordinated immunometabolic activation involving IL-1RA, IFN-α2, and irisin. Ferritin burden may identify a subgroup of children with altered antiviral immune status and suppressed irisin response. These findings support further molecular studies using JCV PCR, viral load assessment, oxidative stress markers, and longitudinal follow-up.