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Serum pro-hepcidin: measuring active hepcidin or a non-functional precursor?
  1. M J Brookes,
  2. N K Sharma,
  3. C Tselepis,
  4. T H Iqbal
  1. City Hospital, Birmingham, UK
  1. Correspondence to:
    Dr M J Brookes
    City Hospital, Dudley Rd, Birmingham B18 7QH, UK; mbro453398aol.com

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We read with great interest the paper “Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia” (Gut 2004;53:735–43) .

We have two observations. Firstly it was shown that pro-hepcidin and hepcidin were colocalised within the liver and in Hep-G cells. However, it was not possible, using serum ELISA, to identify the C terminus of hepcidin (the mature form of hepcidin 25). Is it possible that the functional N terminal antibody used for serum analyses represents non-functional precursor amino acids and not the active molecule? This might explain the lack of correlation between iron parameters and hepcidin seen from the patient data.

Furthermore, the authors comment on the paradoxically elevated levels of pro-hepcidin in patients with chronic renal insufficiency on erythropoietin (EPO). All of these patients were reported to have normal haemoglobin levels. Previous studies have shown that EPO inhibits hepatic hepcidin expression.1 The authors speculate that the elevated circulating hepcidin levels may reflect reduced renal clearance of the molecule in these patient. However, other studies have suggested chronic inflammatory diseases are associated with elevated serum hepcidin (in animal models)2 and urine hepcidin in humans.3 Another possibility, therefore, is that patients have elevated iron stores, in relation to chronic disease, and this may have a direct effect on hepcidin release. It would be interesting to know the iron metabolic parameters in these patients, as obviously haemoglobin in isolation is not an accurate measure of iron stores. It is unclear from the paper whether fig 8 represents data from patients with haemochromatosis only or all patients studied (as implied in the last paragraph of the results). If the latter is the case it would be very interesting to separate the renal patient data from that of the haemochromatosis patients in whom hepcidin expression is likely to be dysregulated due to direct effects of the HFE gene product.

Clearly future clinical studies in this field hold much promise.

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