PATHOGENESIS
Iron
overload has been implicated as the main precipitating factor of immune
deficiency in β-thalassemia. It constitutes a
primary complication of both thalassemia itself and the therapy, leading to
numerous abnormalities, some of which prove fatal in the course of the disease.
The most important of these include cardiac failure,
hepatic
damage, and endocrine abnormalities, such as hypogonadism, hypothyroidism,
hypoparathyroidism, and diabetes mellitus [1]. Iron overload results from :
– multiple blood transfusions;
– premature intramedullar death of
erythrocytes;
– so-called ineffective
erythropoiesis, which is the hallmark
of thalassemia;
– increased peripheral destruction of
red cells;
– increased intestinal iron
absorption, a compensatory
reaction induced by chronic anemia [1,16].
Insofar
as immune function is concerned, it is believed that iron and its binding
proteins have immunoregulatory properties, and therefore iron excess may tip
the immune balance unfavorably to allow increased growth rates of infectious
organisms [17]. Indeed, immune system abnormalities that have been described in
association with conditions characterized by increased iron load, such as
hemochromatosis and thalassemia, include decreased phagocytosis by the monocyte
– macrophage system, alterations in
T-lymphocyte subsets, with enhancement of CD8 and suppression of CD4,
impairment of immunoglobulin secretion, and suppression of complement system
function [17–20]. It has been
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