| Assessment of natural killer cell subpopulations in pediatric patients with transfusion-dependent β-thalassemia major |
Fathia Elbassal1, Mohamed Soliman1, Nourhan Mohamed1, Mai El-Hamid2, Hanan El-Sheity1 
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1Clinical pathology Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt
2Pediatrics Department, Faculty of Medicine, Menoufia University, Shebin Elkom, Egypt |
Correspondence:
Hanan El-Sheity, Email: hanan_elsheity66@yahoo.com
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Received: 8 May 2025 • Revised: 29 June 2025 • Accepted: 30 June 2025 |
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| Abstract |
Background
Iron overload is a hallmark complication in patients with transfusion-dependent β-thalassemia major, primarily resulting from ineffective erythropoiesis, repeated blood transfusions, and increased gastrointestinal iron absorption. This iron accumulation, reflected in elevated serum ferritin levels, has been implicated in immune dysregulation. Natural killer (NK) cells are a pivotal component of the innate immune system, known for their cytotoxic activity and cytokine secretion, particularly interferon-gamma (IFN-γ). Disruption in NK cell subsets may compromise immune surveillance and defense against infections in these patients.
Purpose
To evaluate the distribution and function of NK cell subpopulations in pediatric patients with transfusion-dependent β-thalassemia major and explore their association with iron overload and immune dysfunction.
Methods
Seventy-eight children were enrolled and divided into 2 groups: 43 pediatric patients with transfusion-dependent β-thalassemia major and 35 apparently healthy controls. NK cells and their subsets (CD56bright, CD56dim, CD56neg) were quantified using multicolor flow cytometry. Serum IFN-γ levels were measured to assess NK cell cytokine activity. Ferritin levels were used as a marker of iron overload.
Results
Patients showed a significant reduction in CD56bright and CD56dim NK cells compared to controls (P<0.001), indicating impaired NK-mediated immunity. Conversely, the CD56neg subset, associated with dysfunctional or altered NK cell phenotypes, was significantly elevated in patients (P<0.002). A strong negative correlation was observed between serum ferritin levels and CD56dim NK cells (P=0.003), suggesting that iron overload suppresses cytotoxic NK activity. Moreover, IFN-γ levels inversely correlated with CD56bright (P<0.001) and CD56dim (P=0.019) cells, but positively correlated with CD56neg cells, implicating this altered subset as a potential compensatory source of cytokine production.
Conclusion
Hyperferritinemia in pediatric β-thalassemia major is linked to a dysregulated NK cell profile, marked by suppression of functional CD56bright and CD56dim subsets and expansion of the atypical CD56neg subset. These alterations may compromise innate immunity and contribute to increased infection risk. Our findings highlight the immunomodulatory impact of iron overload and underscore the clinical importance of monitoring NK cell dynamics in thalassemia management. |
| Key Words:
Natural killer cells, Thalassemia, Hyperferritinemia |
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