Development of a molecular-clinical predictive model for iron overload complications in beta-thalassemia major: Integrating transferrin receptor-2, ferroportin, soluble transferrin receptor, and toxic iron species (nontransferrin-bound iron)

BACKGROUND: Beta-thalassemia major (β-TM) is a hereditary blood disorder requiring lifelong blood transfusions, which result in iron overload and progressive organ damage. Iron chelation therapy is therefore essential to reduce excess iron and its complications. OBJECTIVES: This study aimed to evaluate the effect of different iron chelation therapies on the expression of iron-regulatory genes and on biochemical markers related to iron metabolism and inflammation in patients with β-TM. MATERIALS AND METHODS: Thirty patients diagnosed with β-TM and 20 healthy controls were enrolled and stratified according to iron chelation therapy, along with a healthy control group for comparison. Expression levels of Transferrin receptor-2 (TFR2) and ferroportin (FPN) were evaluated by the polymerase chain reaction. Serum concentrations of interleukin-6 (IL-6), soluble TFR (sTFR), nontransferrin-bound iron (NTBI), cortisol, thyroid stimulating hormone (TSH), and ferritin were determined using the standard biochemical methods. RESULTS: The expression of the TFR2 gene and serum IL6 was statistically significant, whereas FPN gene showed no statistically change. The treatment elevated cortisol levels; however, the alteration was not statistically significant. sTFR, NTBI, TSH, and ferritin all showed that there was too much iron in the body, however, some comparisons did not show any big differences. CONCLUSIONS: It can be concluded that iron chelation therapy, particularly deferasirox, is related to the extent of TFR2 gene expression and IL-6 levels and changes in terms of iron metabolism and inflammation activity in β-TM patients. TFR2 and IL-6 showed significant alterations and may represent potential indicators of iron overload in β-thalassemia major patients.