Novel Circulating isoforms of hepcidin

Morten Moe1, Tor-Arne Hagve1,*, Ingrid M Hardang1

1Unit of Medical Biochemistry, Division of Diagnostics and Technology, Akershus University Hospital, Lorenskog, Norway

Introduction: Hepcidin-25 (Hep25) is a key regulator of iron metabolism. Two circulating isoforms of hepcidin are known, Hep22 and Hep20, where only the latter has been reported to exist in blood. The biological functions of the isoforms are not known. We have recently established a method for hepcidin analysis based on liquid chromatography-mass spectrometry, and during that work, we have discovered novel circulating isoforms of hepcidin.

Objectives: To identify the circulating isoforms of hepcidin.

Methods: Hepcidin was isolated from serum by solid phase extraction. The extract was analysed by high performance liquid chromatography coupled to high resolution tandem mass spectrometry.

Results: We found Hep25 and its isoforms Hep22 and Hep20 in serum. In addition, we also discovered Hep24 Hep23, and Hep19 (the former has later also been reported by others). The circulating concentrations of the novel isoforms were high in sera that also were high in hepcidin-25. The total concentration of the isoforms varies between 5 and 50% of that of Hep25.

Conclusion: We have established hepcidin analysis in our laboratory, and in serum samples with Hep25 concentration >10 ng/mL we frequently also observe the isoforms Hep24, -22, and 20. The isoforms Hep19 and -23 are less frequently observed. Patients with an infection have high Hep25 concentrations, whereas there is no correlation between circulating concentration of Hep25 and disease severity in patients with SLE 

Keywords: Biomarker development