A Rapid and Sensitive Assay to Measure Hepcidin Levels in Biological Fluids
Hepcidin is a liver-produced peptide hormone which controls iron absorption by regulating the amount of the cell surface iron transporter ferroportin, which exports iron from cells to blood. Altered hepcidin levels are associated with disorders of iron metabolism and absorption, and disease-associated anemia. Hepcidin also plays an important role in regulation of innate immunity and inflammation. Therapeutic modulation of hepcidin levels could also provide a new approach for the treatment of iron-dependent disorders.
Previously, the detection and quantification of hepcidin for diagnostic purposes has been difficult due to challenges in production of specific antibodies, and their lack of specificity for the intact and bioactive form of hepcidin. Based on the identification of a high-affinity hepcidin binding domain on ferroportin, the present invention provides a rapid and sensitive assay to measure hepcidin levels in biological fluids, providing a valuable clinical and diagnostic tool for diseases related to iron metabolism and inflammation.
Hepcidin deficiency is the primary cause of hereditary hemochromatosis, a disease characterized by excessive iron absorption, while excess hepcidin contributes to the pathology of iron-loading anemias such as thalassemia major. In addition, hepcidin levels are increased in patients with anemia of inflammation, acute infection, and severe sepsis. In a recent study, excess hepcidin was also found to accumulate in the serum of patients receiving hemodialysis, indicating that it could contribute to the pathogenesis of renal anemia and serve as a biomarker for diagnosis of this condition. Accurate detection of hepcidin levels would be a useful clinical tool for diagnosis and assessment of these and other diseases involving inflammation, anemia, or iron overload.
� De Domenico I, Ward DM, Langelier C, Vaughn MB, Nemeth E, Sundquist WI, Ganz T, Musci G, Kaplan J. (2007) The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol. Biol. Cell.
Jerry Kaplan, Diane McVey Ward, Ivana de Domenico
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