VEGF and Pentraxin-3 Expression in β-Thalassemia Major: Links Between Innate Immune Activation, Endothelial Damage, and Calcium Metabolism Disturbances

Background: Transfusion-dependent β-thalassemia (TDT) is commonly associated with vascular and endocrine complications, including hypoparathyroidism (HPT). Dysregulated angiogenesis and innate immune activation—reflected by vascular endothelial growth factor (VEGF) and pentraxin-3 (PTX3)—may contribute to endothelial dysfunction and altered calcium–phosphate balance. Objective: This study aimed to examine serum levels and mRNA expression of VEGF and PTX3 in patients with β-thalassemia major and to explore their relationship with endothelial injury, mineral disturbances, and HPT. Methodology: One hundred subjects were included: 50 healthy controls and 50 patients with β-thalassemia major (38 with normal parathyroid function and 12 with HPT). Serum VEGF and PTX3 were measured by ELISA, and gene expression was assessed using RT-qPCR. Correlation analyses and ROC curves were performed to evaluate associations and predictive performance. Results: Compared with controls, patients with β-thalassemia major had significantly elevated serum and mRNA expression levels of VEGF and PTX3 (p < 0.001). Within the patient group, those with HPT showed markedly higher levels than individuals with preserved parathyroid function (p < 0.001). VEGF and PTX3 correlated positively with serum phosphate and negatively with parathyroid hormone (p < 0.001). ROC analysis demonstrated good predictive accuracy for HPT: VEGF (AUC = 0.838; sensitivity 83%; specificity 74%) and PTX3 (AUC = 0.814; sensitivity 83%; specificity 71%). Conclusion: VEGF and PTX3 are significantly upregulated in β-thalassemia major, particularly in HPT, reflecting intertwined endothelial and innate immune activation with disordered mineral metabolism. They may serve as useful biomarkers of vascular and parathyroid dysfunction in TDT.