Pathogenetic aspects of immune deficiency associated with beta-thalassemia.
Infectious complications constitute the second most common cause of mortality and a main cause of morbidity in beta-thalassemia. Besides the high risk of blood-borne infections associated with multiple transfusions, the increased susceptibility of these patients to infectious diseases has been attributed to a coexistent immune deficiency. Immune abnormalities have also been held responsible for the frequent occurrence of malignancies in beta-thalassemia, especially leukemia and lymphomas. Recent studies on immune competence in beta-thalassemia have revealed numerous quantitative and functional defects, involving T and B lymphocytes, immunoglobulin production, neutrophils and macrophages, chemotaxis, and phagocytosis, as well as the complement system. Regarding pathogenesis, iron overload, a primary complication of both thalassemia itself and transfusion therapy, is thought to be the main precipitating mechanism, due to the important immunoregulatory properties of iron and its binding proteins; iron excess may derange the immune balance in favor of the growth of infectious organisms. Other factors include multiple transfusions, associated with constant allo-antigenic stimulation, as well as with transmission of immunosuppressive viruses; splenectomy, resulting in increased susceptibility to infections by encapsulated bacteria and to immune system modifications; low levels of zinc, another immune regulator; iron chelation therapy, which predisposes to serious infections by yersinia species; and the circulation of abnormal native thalassemic erythrocytes, forming another permanent immune stimulus. Thus surveillance for infections in patients with beta-thalassemia is crucial, while further studies are warranted on immune function abnormalities and the implicated mechanisms.
Farmakis
Dimitrios
D
1st Department of Internal Medicine, Laiko General Hospital, School of Medicine, University of Athens, Athens, Greece. dfarm@panafonet.gr
Giakoumis
Anastasios
A
Polymeropoulos
Evaggelos
E
Aessopos
Athanasios
A
D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology; D007501:Iron / Q000378:metabolism; D017086:beta-Thalassemia / Q000150:complications / Q000276:immunology* / Q000473:pathology*
D007501:Iron