title: The soluble transferrin receptor as a marker of iron homeostasis in normal subjects and in HFE-related hemochromatosis.
abstract: OBJECTIVE
  The soluble transferrin receptor (sTfR) is a clinical marker of erythropoietic activity, also used in the diagnosis of iron deficiency. In the present paper we explore the meaning of this parameter in normal physiological conditions of iron homeostasis and in the setting of iron overload due to hereditary hemochromatosis (HH).
  
  
  METHODS
  Reference values for sTfR were established in a population of 42 apparently healthy subjects, analyzed in relation to other hematologic parameters, namely, hemoglobin (Hb), mean corpuscular volume (MCV), transferrin saturation (TfSat) and serum ferritin. The same analysis was done in a group of 45 patients with HH who were homozygous for the C282Y mutation of HFE and had a wide range of TfSat values. In addition, individual serial profiles were analyzed in three patients.
  
  
  RESULTS
  In normal subjects circulating sTfR correlated significantly with the TfSat level, reflecting the systemic effect of iron availability on the erythropoietic activity in a normal physiological steady state. A TfSat of 25% appeared as a threshold value, below which there was a progressive increase in sTfR; this increase in sTfR occurred concomitantly with a decrease in Hb, MCV and serum ferritin. In HH patients the up-regulation of sTfR started at TfSat values as high as 50%.
  
  
  CONCLUSIONS
  The fact that sTfR up-regulation started at higher TfSat values in HH patients suggests that the recognition of systemic iron available for erythropoiesis is altered in this condition. Based on these results, a new hypothesis is advanced, proposing that the HFE protein in involved as a sensor of systemic iron availability, via the soluble transferrin receptor.
authors.affiliation: ICBAS, Abel Salazar Institute for the Biomedical Sciences, Porto, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Brandão
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Oliveira
authors.forename: Fernanda
authors.initials: F
authors.lastname: Bravo
authors.forename: Júlia
authors.initials: J
authors.lastname: Reis
authors.forename: Isabel
authors.initials: I
authors.lastname: Garrido
authors.forename: Graça
authors.initials: G
authors.lastname: Porto
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D004909:Erythrocyte Indices; D005260:Female; D006432:Hemochromatosis / Q000097:blood* / Q000235:genetics*; D000071020:Hemochromatosis Protein; D006454:Hemoglobins / Q000032:analysis; D015395:Histocompatibility Antigens Class I / Q000097:blood* / Q000235:genetics*; D006706:Homeostasis; D006801:Humans; D007501:Iron / Q000378:metabolism*; D016014:Linear Models; D008297:Male; D008565:Membrane Proteins / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D011990:Receptors, Transferrin / Q000097:blood*; D012995:Solubility
chemical_list: D015415:Biomarkers; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D006454:Hemoglobins; D015395:Histocompatibility Antigens Class I; D008565:Membrane Proteins; D011990:Receptors, Transferrin; D007501:Iron