Origa Raffaella, Galanello Renzo, Ganz Tomas, Giagu Nicolina, Maccioni Liliana, Faa Gavino, Nemeth Elizabeta
Dipartimento di Scienze Biomediche e Biotecnologie, Università di Cagliari, Ospedale Microcitemico ASL8- Cagliari, Italy.
Haematologica. 2007 May;92(5):583-8. doi: 10.3324/haematol.10842.
Patients with beta-thalassemia, like those with genetic hemochromatosis, develop iron overload due to increased iron absorption, and their iron burden is further exacerbated by transfusion therapy. Hepcidin, a hepatic hormone, regulates systemic iron homeostasis by inhibiting the absorption of iron from the diet and the recycling of iron by macrophages. In turn, hepcidin release is increased by iron loading and inhibited by erythropoietic activity. Hepcidin deficiency is the cause of iron overload in most forms of hereditary hemochromatosis. We sought to determine hepcidin's role in the pathogenesis of iron overload in b-thalassemia.
We assessed the degree of iron overload in thalassemia intermedia and major patients by measuring hepatic iron concentration in liver biopsy samples and serum ferritin, estimated erythropoietic drive by assaying soluble transferrin receptor and serum erythropoietin levels and correlated these with urinary hepcidin measurements.
Urinary hepcidin levels in beta-thalassemia demonstrate severe hepcidin deficiency in thalassemia intermedia. There was a strong inverse relationship between urinary hepcidin levels and both erythropoietin and soluble transferrin receptor, markers of erythropoietic activity. In contrast, hepcidin levels were elevated in thalassemia major, presumably due to transfusions that reduce erythropoietic drive and deliver a large iron load. Despite similar liver iron concentrations in the two conditions, serum ferritin was much lower in thalassemia intermedia.
In thalassemia intermedia, high erythropoietic drive causes severe hepcidin deficiency. The lack of hepcidin results in hyperabsorption of dietary iron, but also in iron depletion of macrophages, lowering their secretion of ferritin and, consequently, serum ferritin levels. In contrast, in thalassemia major, transfusions decrease erythropoietic drive and increase the iron load, resulting in relatively higher hepcidin levels. In the presence of higher hepcidin levels, dietary iron absorption is moderated and macrophages retain iron, contributing to higher serum ferritin. In the future, hepcidin measurements may allow a more accurate assessment of the degree of iron overload and the maldistribution of iron in thalassemia.
β地中海贫血患者与遗传性血色素沉着症患者一样，因铁吸收增加而出现铁过载，输血治疗会进一步加重其铁负荷。铁调素是一种肝脏激素，通过抑制饮食中铁的吸收以及巨噬细胞对铁的再循环来调节全身铁稳态。反过来，铁调素的释放会因铁负荷增加而增加，因红细胞生成活性而受到抑制。铁调素缺乏是大多数遗传性血色素沉着症形式中铁过载的原因。我们试图确定铁调素在β地中海贫血铁过载发病机制中的作用。
我们通过测量肝活检样本中的肝脏铁浓度和血清铁蛋白来评估中间型和重型地中海贫血患者的铁过载程度，通过检测可溶性转铁蛋白受体和血清促红细胞生成素水平来估计红细胞生成驱动力，并将这些与尿铁调素测量值相关联。
β地中海贫血患者的尿铁调素水平显示中间型地中海贫血存在严重的铁调素缺乏。尿铁调素水平与促红细胞生成素和可溶性转铁蛋白受体（红细胞生成活性标志物）之间存在强烈的负相关关系。相比之下，重型地中海贫血中铁调素水平升高，可能是由于输血减少了红细胞生成驱动力并带来大量铁负荷。尽管两种情况下肝脏铁浓度相似，但中间型地中海贫血患者的血清铁蛋白要低得多。
在中间型地中海贫血中，高红细胞生成驱动力导致严重的铁调素缺乏。铁调素的缺乏导致饮食中铁的过度吸收，但也导致巨噬细胞铁耗竭，降低了它们的铁蛋白分泌，从而降低了血清铁蛋白水平。相比之下，在重型地中海贫血中，输血降低了红细胞生成驱动力并增加了铁负荷，导致铁调素水平相对较高。在铁调素水平较高的情况下，饮食中铁的吸收受到调节，巨噬细胞保留铁，导致血清铁蛋白升高。未来，铁调素测量可能有助于更准确地评估地中海贫血中铁过载的程度和铁的分布不均。
