Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women

Abstract

Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients undergoing phlebotomy treatment, or pregnant women Hepcidin plays a major role in iron homeostasis, but understanding its role has been hampered by the absence of analytical methods for quantification in blood. A commercial ELISA has been developed for serum prohepcidin, a hepcidin precursor, and there is interest in its potential use in the clinical and research arena. We investigated the association between serum prohepcidin concentration and iron absorption in healthy men, and its relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis patients, and pregnant women. Iron absorption was determined in thirty healthy men (fifteen wild-type, fifteen C282Y heterozygote) using the stable isotope red cell incorporation technique. Iron status was measured in 138 healthy men (ninety-one wild-type, forty-seven C282Y heterozygote), six hereditary haemochromatosis patients, and thirteen pregnant women. Mean serum prohepcidin concentrations were 214 (SD 118) ng/ml [208 (SD 122) ng/ml in wild-type and 225 (SD 109) ng/ml in C282Y heterozygotes] in healthy men, 177 (SD 36) ng/ml in haemochromatosis patients, and 159 (SD 59) ng/ml in pregnant women. There was no relationship between serum prohepcidin concentration and serum ferritin in any subject groups, nor was it associated with efficiency of iron absorption. Serum prohepcidin is not a useful biomarker for clinical or research purposes. Hepcidin plays a major role in iron homeostasis, but full characterisation of its role in healthy humans and patients has been hindered by the absence of analytical methods to quantify circulating levels in the blood. Quantification of mRNA in the liver has been undertaken using reverse transcription and the polymerase chain reaction (Bridle et al. 2003;Gehrke et al. 2003), and polyclonal antibodies to refolded synthetic hepcidin have been produced and used for quantification in urine (Nemeth et al. 2003). Attempts to produce correctly folded synthetic hepcidin have proved difficult because the sequence contains eight cysteine residues that constrain the hepcidin molecule in a hairpin structure (Hunter et al. 2002). Hepcidin in urine has also been quantified using mass spectrometry methods (Kemna et al. 2005;Liang et al. 2006;Tomosugi et al. 2006).Prohepcidin, the sixty-amino-acid product of cleavage of the signal peptide from the hepcidin precursor, is expressed at the basolateral membrane domain of hepatocytes and is found in blood (Kulaksiz et al. 2004). Serum prohepcidin concentrations are significantly lower in patients with hereditary haemochromatosis compared to healthy control subjects (Kulaksiz et al. 2004), increase with declining kidney function (Taes et al. 2004), and are correlated with haematocrit in chronic haemodialysis patients (Hsu et al. 2006), but it is currently unclear whether * Corresponding author: ...

Serum Prohepcidin and Hepcidin Levels in Patients with Ankylosing Spondylitis: A Prospective Study

“…Furthermore, Nagashima et al reported that serum levels of prohepcidin negatively correlated with levels of ferritin in patients with viral hepatitis C, while this correlation was positive in patients with viral hepatitis B and healthy controls [23]. On the other hand, in other studies serum levels of prohepcidinwere reported as unrelated with ferritin or other iron parameters [24,25]. In our study, no significant difference in serum levels of ferritin was found between healthy controls and patients with AS.…”

“…Serum levels of ferritin increases as acute phase reactant in AS. Hepcidin is known to be closely associated and positively correlated with ferritin [9,18] but there are also reports of correlation between prohepcidin and ferritin levels [17,[23][24][25]. A positive correlation was demonstrated between serum levels of prohepcidin and ferritin in chronic renal failure [17].…”

Hepcidin for Clinicians

“…Because of concerns that a urine assay would not be accurate in CKD, the first published studies in CKD used serum prohepcidin as a surrogate for bioactive hepcidin (22)(23)(24). Prohepcidin was found to be elevated in patients with CKD and inversely correlated with GFR (23-25); however, prohepcidin had minimal interaction with iron or inflammatory parameters in CKD (23,24,26,27) and patients without CKD (28,29). This may be explained by prohepcidin being an intermediate metabolite without physiologic activity.…”

Serum Prohepcidin Levels in Children with Thalassemia Major and Intermedia

“…It is not clear whether the serum prohepcidin level measures the active hepcidin or whether there is a functional precursor. Changes in the level of serum prohepcidin have been reported to fail to reflect the iron status exactly (11,19,20). Serum prohepcidin levels were not found to be statistically significant difference compared to the control group in patients with high ferritin levels with hereditary hemochromatosis and sickle cell anaemia (19,20).…”

“…Changes in the level of serum prohepcidin have been reported to fail to reflect the iron status exactly (11,19,20). Serum prohepcidin levels were not found to be statistically significant difference compared to the control group in patients with high ferritin levels with hereditary hemochromatosis and sickle cell anaemia (19,20). Similarly, Kulaksiz et al (11) did not find any relationship of serum prohepcidin levels with serum iron, transfer saturation, and serum ferritin levels.…”