Department of Medicine, University of Verona, Policlinico GB Rossi, 37134 Verona, Italy.
Haematologica. 2011 Apr;96(4):500-6. doi: 10.3324/haematol.2010.033449. Epub 2010 Dec 20.
Inadequate hepcidin production leads to iron overload in nearly all types of hemochromatosis. We explored the acute response of hepcidin to iron challenge in 25 patients with HFE-hemochromatosis, in two with TFR2-hemochromatosis and in 13 controls. Sixteen patients (10 C282Y/C282Y homozygotes, 6 C282Y/H63D compound heterozygotes) had increased iron stores, while nine (6 C282Y/C282Y homozygotes, 3 C282Y/H63D compound heterozygotes) were studied after phlebotomy-induced normalization of iron stores.
We analyzed serum iron, transferrin saturation, and serum hepcidin by both enzyme-linked immunosorbent assay and mass-spectrometry at baseline, and 4, 8, 12 and 24 hours after a single 65-mg dose of oral iron.
Serum iron and transferrin saturation significantly increased at 4 hours and returned to baseline values at 8-12 hours in all groups, except in the iron-normalized patients who showed the highest and longest increase of both parameters. The level of hepcidin increased significantly at 4 hours and returned to baseline at 24 hours in controls and in the C282Y/H63D compound heterozygotes at diagnosis. The hepcidin response was smaller in C282Y-homozygotes than in controls, barely detectable in the patients with iron-depleted HFE-hemochromatosis and absent in those with TFR2-hemochromatosis. Conclusions Our results are consistent with a scenario in which TFR2 plays a prominent and HFE a contributory role in the hepcidin response to a dose of oral iron. In iron-normalized patients with HFE hemochromatosis, both the low baseline hepcidin level and the weak response to iron contribute to hyperabsorption of iron.
铁调素生成不足会导致几乎所有类型的血色病中铁过载。我们在 25 名 HFE 血色病患者、2 名 TFR2 血色病患者和 13 名对照者中,探索了铁负荷对铁调素的急性应答。16 名患者(10 名纯合子 C282Y/C282Y,6 名复合杂合子 C282Y/H63D)有铁储存增加,9 名(6 名纯合子 C282Y/C282Y,3 名复合杂合子 C282Y/H63D)在放血后铁储存正常时研究。
我们用酶联免疫吸附试验和质谱法,在基线时以及单次口服 65mg 铁后 4、8、12 和 24 小时,分析血清铁、转铁蛋白饱和度和血清铁调素。
除铁储存正常的患者外,所有组的血清铁和转铁蛋白饱和度在 4 小时显著增加,并在 8-12 小时恢复到基线值,在铁储存正常的患者中,这两个参数的升高最高且持续时间最长。在对照组和诊断时 C282Y/H63D 复合杂合子中,铁调素在 4 小时显著增加,并在 24 小时恢复到基线。C282Y 纯合子的铁调素反应小于对照组,铁缺乏的 HFE 血色病患者几乎检测不到,TFR2 血色病患者则检测不到。结论:我们的结果与以下情况一致,即 TFR2 在铁调素对口服铁剂量的应答中起主要作用,HFE 起辅助作用。在铁储存正常的 HFE 血色病患者中,低基线铁调素水平和对铁的弱应答导致铁的过度吸收。