Clinical Immunoassay for Human Hepcidin Predicts Iron Deficiency in First-Time Blood Donors
Overview
Authors
Affiliations
Background: Serum markers currently used as indicators of iron status have clinical limitations. Hepcidin, a key regulator of iron homeostasis, is reduced in iron deficiency (ID) and increased in iron overload. We describe the first CLIA-validated immunoassay with excellent accuracy and precision to quantify human serum hepcidin. Its diagnostic utility for detecting ID in first-time blood donors was demonstrated.
Methods: A monoclonal competitive ELISA (C-ELISA) was developed for the quantitation of human hepcidin and validated according to CLIA guidelines. Sera from nonanemic first-time blood donors (n = 292) were analyzed for hepcidin, ferritin, transferrin, and serum iron. Logistic regression served to determine the utility of hepcidin as a predictor of ID.
Results: The C-ELISA was specific for human hepcidin and had a low limit of quantitation (4.0 ng/mL). The hepcidin concentration measured with the monoclonal C-ELISA was strongly correlated with a previously established, extensively tested polyclonal C-ELISA (Blood 2008;112:4292-7) (r = 0.95, P < 0.001). The area under the receiver operating characteristic curve for hepcidin as a predictor of ID, defined by 3 ferritin concentration thresholds, was >0.9. For predicting ID defined by ferritin <15 ng/mL, hepcidin <10 ng/mL yielded sensitivity of 93.1% and specificity of 85.5%, whereas the same hepcidin cutoff for ferritin <30 ng/mL yielded sensitivity of 67.6% and specificity of 91.7%.
Conclusion: The clinical measurement of serum hepcidin concentrations was shown to be a potentially useful tool for diagnosing ID.
Barad A, Xu Y, Bender E, Pressman E, Gu Z, OBrien K Am J Clin Nutr. 2025; 121(2):406-416.
PMID: 39909710 PMC: 11863331. DOI: 10.1016/j.ajcnut.2024.10.018.
Baldi A, Braat S, Hasan M, Bennett C, Barrios M, Jones N Nat Commun. 2024; 15(1):8640.
PMID: 39367018 PMC: 11452624. DOI: 10.1038/s41467-024-53013-x.
Gonzalez-Fernandez D, Nemeth E, Pons E, Rueda D, Sinisterra O, Murillo E Nutrients. 2024; 16(11).
PMID: 38892681 PMC: 11174717. DOI: 10.3390/nu16111748.
REDD1 deletion and treadmill running increase liver hepcidin and gluconeogenic enzymes in male mice.
Barney Jr D, Gordon B, Hennigar S J Nutr Sci. 2023; 12:e49.
PMID: 37123395 PMC: 10131055. DOI: 10.1017/jns.2023.37.