title: A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis.
abstract: 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.
  
  
  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 HFE hemochromatosis, both the low baseline hepcidin level and the weak response to iron contribute to hyperabsorption of iron.
authors.affiliation: Department of Medicine, University of Verona, Policlinico GB Rossi, 37134 Verona, Italy. domenico.girelli@univr.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Girelli
authors.forename: Paola
authors.initials: P
authors.lastname: Trombini
authors.forename: Fabiana
authors.initials: F
authors.lastname: Busti
authors.forename: Natascia
authors.initials: N
authors.lastname: Campostrini
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
authors.forename: Sara
authors.initials: S
authors.lastname: Pelucchi
authors.forename: Mark
authors.initials: M
authors.lastname: Westerman
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Elizabeta
authors.initials: E
authors.lastname: Nemeth
authors.forename: Alberto
authors.initials: A
authors.lastname: Piperno
authors.forename: Clara
authors.initials: C
authors.lastname: Camaschella
mesh_terms: D000328:Adult; D023181:Antimicrobial Cationic Peptides / Q000097:blood*; D005293:Ferritins / Q000097:blood; D005838:Genotype; D006432:Hemochromatosis / Q000097:blood* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007501:Iron / Q000008:administration & dosage* / Q000097:blood* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000235:genetics; D013997:Time Factors
chemical_list: D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D064451:Hepcidins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; C503640:TFR2 protein, human; D005293:Ferritins; D007501:Iron