Phenotypical and functional abnormalities of circulating neutrophils in patients with ß-thalassemia.

ß-Thalassemia is an inherited single gene disorder related to reduced synthesis of the ß-globin chain of hemoglobin. Patients with ß-thalassemia present variable clinical severity ranging from asymptomatic trait to severe transfusion-dependent anemia and multiple organs complications. Moreover, multiple immune abnormalities are a major concern in ß-thalassemia patients. Aberrant neutrophil effector function plays a pivotal role in infection susceptibility in these patients. In severe and persistent inflammation, immature neutrophils are released from the bone marrow and are functionally different compared with mature ones. Despite some abnormalities reported for thalassemia patient's immune system, few data exist on the characterization of human neutrophils in ß-thalassemia. The aim of this study was to investigate the phenotype and function of circulating neutrophil subsets in patients with ß-thalassemia major and with ß-thalassemia intermedia divided in transfusion-dependent and non-transfusion-dependent. By the use of immunochemical and cytofluorimetric analyses, we observed that patients' CD16+ neutrophils exhibit abnormalities in their phenotype and functions and the abnormalities vary according to the clinical form of the disease and to the neutrophil subset (CD16bright and CD16dim). Abnormalities include altered surface expression of the innate immune receptor CD45, Toll-like receptor 4, and CD32, reduced ability to produce an oxidative burst, and elevated levels of membrane lipid peroxidation, especially in patients with a more severe form of the disease. Overall, our results indicating the occurrence of an immuno-senescent phenotype on circulating neutrophils from thalassemia patients suggest the usefulness of neutrophil feature assessment as a tool for better clinical management of ß-thalassemia.

HCV Infection in Thalassemia Syndromes and Hemoglobinopathies: New Perspectives.

Hepatitis C virus (HCV) infection is one of the most serious complications of transfusion therapy in the thalassemia and sickle cell disease (SCD) population before 1990; in fact, since 1990 serological tests were made available to detect infection in blood donors. The iron chelation therapy has improved the life expectancy of these patients and, consequently, a decrease in death due to heart disease may be observed, as well as an increase in liver disease due to the iron overload and HCV infection that lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Until few years ago, the recommended therapy for HCV treatment consisted of pegylated-interferon alpha plus ribavirin, a therapy with important side effects. This treatment has been severely limited to thalassemic and SCD patients due to the hemolytic anemia induced by ribavirin causing an increase in the number of blood transfusions. The development of highly effective Direct-acting Antiviral Agents toward different viral genotypes has led to a real HCV eradication with negative viremia and sustained viral response between 90 and 98%. At the beginning some indications of Direct-acting Antiviral Agents administration were available for those patients exhibiting advanced cirrhosis or needing liver transplantation over time for the high costs of the new drugs. Recently, all treatment regimens can be used for patients with various HCV genotypes, different stages of liver disease, and comorbidities. The HCV eradication has also led to a marked improvement in the parameters of martial accumulation, demonstrating a synergic action also between the effect of antiviral therapy and iron chelation.