Kearney Susan L, Nemeth Elizabeta, Neufeld Ellis J, Thapa Dharma, Ganz Tomas, Weinstein David A, Cunningham Melody J
Division of Hematology/Oncology, Children's Hospital, Boston, Massachusetts, USA.
Pediatr Blood Cancer. 2007 Jan;48(1):57-63. doi: 10.1002/pbc.20616.
Hepcidin, a regulator for iron homeostasis, is induced by inflammation and iron burden and suppressed by anemia and hypoxia. This study was conducted to determine the hepcidin levels in patients with congenital chronic anemias.
Forty-nine subjects with anemia, varying degrees of erythropoiesis and iron burden were recruited. Eight children with immune thrombocytopenia were included as approximate age-matched controls. Routine hematologic labs and urinary hepcidin (uhepcidin) levels were assessed. For thalassemia major (TM) patients, uhepcidin was obtained pre- and post-transfusion.
In TM, uhepcidin levels increased significantly after transfusion, demonstrated wide variance, and the median did not significantly differ from controls or thalassemia intermedia (TI). In both thalassemia syndromes, the hepcidin to ferritin ratio, a marker of the appropriateness of hepcidin expression relative to the degree of iron burden, was low compared to controls. In TI and sickle cell anemia (SCA), median uhepcidin was low compared to controls, P = 0.013 and <0.001, respectively. In thalassemia subjects, uhepcidin levels were positively associated with ferritin. In subjects with SCA, uhepcidin demonstrated a negative correlation with reticulocyte count.
This study examines hepcidin levels in congenital anemias. In SCA, hepcidin was suppressed and inversely associated with erythropoietic drive. In thalassemic syndromes, hepcidin was suppressed relative to the degree of iron burden. Transfusion led to increased uhepcidin. In thalassemia, the relative influence of known hepcidin modifiers was more difficult to assess. In thalassemic syndromes where iron overload and anemia have opposing effects, the increased erythropoietic drive may positively influence hepcidin production.
铁调素是铁稳态的调节因子，受炎症和铁负荷诱导，受贫血和缺氧抑制。本研究旨在测定先天性慢性贫血患者的铁调素水平。
招募了49名患有不同程度贫血、红细胞生成和铁负荷的受试者。纳入8名免疫性血小板减少症儿童作为年龄匹配的对照。评估常规血液学检查指标和尿铁调素（uhepcidin）水平。对于重型地中海贫血（TM）患者，在输血前后检测uhepcidin。
在TM患者中，输血后uhepcidin水平显著升高，呈现出较大差异，且中位数与对照组或中间型地中海贫血（TI）无显著差异。在两种地中海贫血综合征中，铁调素与铁蛋白的比值（铁调素表达相对于铁负荷程度的适宜性指标）与对照组相比均较低。在TI和镰状细胞贫血（SCA）中，uhepcidin中位数与对照组相比均较低，P值分别为0.013和<0.001。在地中海贫血受试者中，uhepcidin水平与铁蛋白呈正相关。在SCA受试者中，uhepcidin与网织红细胞计数呈负相关。
本研究检测了先天性贫血患者的铁调素水平。在SCA中，铁调素受到抑制，且与红细胞生成驱动力呈负相关。在地中海贫血综合征中，相对于铁负荷程度，铁调素受到抑制。输血导致uhepcidin升高。在地中海贫血中，已知铁调素调节因子的相对影响更难评估。在铁过载和贫血具有相反作用的地中海贫血综合征中，增加的红细胞生成驱动力可能对铁调素产生有积极影响。
