Immunoassay for human serum hepcidin.
We developed and validated the first serum enzyme-linked immunosorbent assay for hepcidin, the principal iron-regulatory hormone that has been very difficult to measure. In healthy volunteers, the 5% to 95% range of hepcidin concentrations was 29 to 254 ng/mL in men (n = 65) and 17 to 286 ng/mL in women (n = 49), with median concentrations 112 versus 65 (P < .001). The lower limit of detection was 5 ng/mL. Serum hepcidin concentrations in 24 healthy subjects correlated well with their urinary hepcidin (r = 0.82). Serum hepcidin appropriately correlated with serum ferritin (r = 0.63), reflecting the regulation of both proteins by iron stores. Healthy volunteers showed a diurnal increase of serum hepcidin at noon and 8 pm compared with 8 am, and a transient rise of serum hepcidin in response to iron ingestion. Expected alterations in hepcidin levels were observed in a variety of clinical conditions associated with iron disturbances. Serum hepcidin concentrations were undetectable or low in patients with iron deficiency anemia (ferritin < 10 ng/mL), iron-depleted HFE hemochromatosis, and juvenile hemochromatosis. Serum hepcidin concentrations were high in patients with inflammation (C-reactive protein > 10 mg/dL), multiple myeloma, or chronic kidney disease. The new serum hepcidin enzyme-linked immunosorbent assay yields accurate and reproducible measurements that appropriately reflect physiologic, pathologic, and genetic influences, and is informative about the etiology of iron disorders.
Ganz
Tomas
T
Intrinsic LifeSciences LLC, La Jolla, CA, USA. tganz@mednet.ucla.edu
Olbina
Gordana
G
Girelli
Domenico
D
Nemeth
Elizabeta
E
Westerman
Mark
M
D018798:Anemia, Iron-Deficiency / Q000097:blood / Q000652:urine; D023181:Antimicrobial Cationic Peptides / Q000097:blood* / Q000652:urine*; D002097:C-Reactive Protein / Q000032:analysis; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005293:Ferritins / Q000097:blood / Q000652:urine; D006432:Hemochromatosis / Q000097:blood / Q000652:urine; D064451:Hepcidins; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000652:urine; D007501:Iron; D007674:Kidney Diseases / Q000097:blood / Q000652:urine; D008297:Male; D009101:Multiple Myeloma / Q000097:blood / Q000652:urine; D012680:Sensitivity and Specificity
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; D064451:Hepcidins; D002097:C-Reactive Protein; D005293:Ferritins; D007501:Iron