Hepcidin modulation in human diseases: from research to clinic

Abstract

By modulating hepcidin production, an organism controls intestinal iron absorption, iron uptake and mobilization from stores to meet body iron need. In recent years there has been important advancement in our knowledge of hepcidin regulation that also has implications for understanding the physiopathology of some human disorders. Since the discovery of hepcidin and the demonstration of its pivotal role in iron homeostasis, there has been a substantial interest in developing a reliable assay of the hormone in biological fluids. Measurement of hepcidin in biological fluids can improve our understanding of iron diseases and be a useful tool for diagnosis and clinical management of these disorders. We reviewed the literature and our own research on hepcidin to give an updated status of the situation in this rapidly evolving field.

Figure 1

Typical mass spectra of human serum (A) and urine (B) samples by SELDI-TOF-MS in a control subject. In addition to hepcidin-25, two isoforms truncated at the N-terminus are detectable. The 20 aa isoform is detectable in both urine and serum, while the 22 aa isoform is found only in urine.

Figure 2

Mean (SE) values of urinary hepcidin (U-hepc), measured as described[20], in patients with different forms of hemochromatosis (A) and in patients with thalassemia major and intermedia (B) compared with healthy controls. Data collected from personal unpublished results and from Barisani et al[67], Cremonesi et al[82], Kattamis et al[90], Matthes et al[116], Nemeth et al[18], Origa et al[91], Papanikolau et al[117], Papanikolau et al[19], Piperno et al[20]. (P < 0.05: Controls vs C282Y +/+) (P < 0.01: Controls vs others; C282Y +/+ vs C282Y/H63D, HJV and Fp; HJV vs Fp; Thalassemia Major vs Intermedia). Statistical analysis was not performed for TFR2 and HAMP due to the small number of patients.