Immunological Investigation of Matrix Metalloproteinases-2 and Tissue Inhibitor of Metalloproteinase-2 in β-Thalassemia Major Patients Infected With Hepatitis C Virus

Abstract

     The levels of Matrix Metalloproteinases-2 (MMP-2) and Tissue Inhibitor of Metalloproteinase-2 (TIMP-2), as well as zinc, iron, and calcium, in patients with β-thalassemia major who undergo repeated blood transfusions, with and without Hepatitis C Virus (HCV) infection, remain unexplored. Many studies have focused on iron overload in β-thalassemia major; however, there is a gap in information regarding the role of MMP-2, both in the presence and absence of HCV infection. The present study focused on the role of MMP-2 and TIMP-2 in β-thalassemia major patients infected with HCV. This cross-sectional observational study included 80 patients suffering from β-thalassemia major; 50 cases had previously been diagnosed as positive for HCV using Enzyme-linked immunosorbent assay (ELISA), and 30 individuals were recorded as negative when using the same technique. Patients aged between 3-48 years had regular blood transfusions and chelation therapy. Sixty healthy individuals were included in this study. Detection of HCV was performed using RT-PCR. ELISA estimated serum levels of MMP-2 and TIMP-2, while calcium, zinc, and iron concentrations were measured using biochemical tests. The receiver operating characteristic (ROC) curve analysis was used to investigate the predictive values of MMP-2 and TIMP-2 for the studied groups. Among ELISA-positive HCV patients, only three individuals (6.0%) showed HCV RNA in their blood samples when RT PCR was used. The mean levels of MMP-2 in HCV-positive and negative β-thalassemia patients were (99.27 ±8.94 and 67.15 ±3.52), respectively, while in the healthy group they were (32.21 ±1.97). The mean levels of TIMP-2 in those patients were (22.91 ±1.54 and 20.29 ±1.22), respectively, and (10.28 ±0.56) for healthy cases. Regarding the mean value of Ca, iron, and Zn, the results were (9.32 ±0.07 for Ca, 341.76 ±11.49 for iron, 67.63 ±3.35 for Zn) and (9.01 ±0.08 for Ca, 284.25 ±8.56 for iron, 59.64 ±3.97 for Zn) in HCV positive and negative β thalassemia patients respectively, while in healthy individuals were (8.71 ±0.07 in Ca, 118.26 ±5.31 in iron, 93.51 ±4.48 in Zn). This study found that infection of β-thalassemia patients with HCV leads to elevated MMP-2 levels, contributing significantly to liver fibrosis through enhanced extracellular matrix breakdown and an inflammatory response. In contrast, TIMP-2, which regulates MMP-2 activity, shows a compensatory increase, reflecting an attempt to balance MMP-2-mediated tissue degradation. This imbalance between MMP-2 and TIMP-2 underscores the accelerated fibrosis seen in these patients.