A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis

作者：Girelli Domenico^*; Trombini Paola; Busti Fabiana; Campostrini Natascia; Sandri Marco; Pelucchi Sara; Westerman Mark; Ganz Tomas; Nemeth Elizabeta; Piperno Alberto; Camaschella Clara

来源：Haematologica-The Hematology Journal, 2011, 96(4): 500-506.

DOI：10.3324/haematol.2010.033449

• hemochromatosis
• hepcidin
• iron challenge
• phlebotomy
• transferrin receptor 2

Background
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.
Design and Methods
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.
Results
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 FIFE hemochromatosis, both the low baseline hepcidin level and the weak response to iron contribute to hyperabsorption of iron.

• 出版日期2011-4