PATHOGENESIS 3

Zinc deficiency is a common feature in β-thalassemia and has also been implicated in the pathophysiology of immune deficiency [28,29]. Like iron, zinc is an immune regulator [28]. The low zinc levels in thalassemic patients have been associated with alterations of lymphocyte subsets and thymulin deficiency. The latter is corrected after zinc supplementation [28].

Splenectomy is a common therapeutic intervention in β- thalassemia, performed to eliminate the increased red blood cell consumption caused by hypersplenism [21]. Besides predisposing to infections by encapsulated bacteria, splenectomy has also been correlated with immune system modifications. These include quantitative lymphocyte changes, though without any functional impairment [30–32], as well as aggravation of the immunological effects of multiple transfusions, due to the reduced immune clearance [12].

Multiple transfusions are thought to be another major pathogenetic mechanism of immune abnormalities. Currently, in most specialized centers transfusion therapy applied to thalassemia major patients consists of hypertransfusion regimens, which aim at maintaining the pretransfusional hemoglobin concentration at 10

g/dl or higher [1,21]. Besides causing iron overload, repetitive transfusions lead to continuous allo-antigenic stimulation, and therefore disturbance of the immune balance. At the same time, they are followed by the risk of transmission of viruses with immunosuppressive properties, such as cytomegalovirus (CMV), Ebstein- Barr virus (EBV) and hepatitis C virus (HCV) [13-27].
In this context, multiple transfusions have been associated with autoimmune hemolysis [22], T- and B-lymphocyte changes[23,24], and modification of monocyte and macrophage functions [13].