Skip to main content
Top
Published in: Journal of Inflammation 1/2017

Open Access 01-12-2017 | Short Report

Evaluation of a competitive hepcidin ELISA assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients

Author: Torbjörn Karlsson

Published in: Journal of Inflammation | Issue 1/2017

Login to get access

Abstract

In this study, a competitive hepcidin ELISA assay was evaluated for its ability to differentiate between iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients, using the absence of stainable bone marrow iron as the diagnostic criterion for iron deficiency. In addition, correlation coefficients for hepcidin versus C-reactive protein, ferritin and interleukin-6 were determined. The optimal cut-off for hepcidin was 21 μg/L, corresponding to sensitivity and specificity of 100% and 67%, respectively, for iron deficiency. For ferritin, a sensitivity and specificity of 91% and 83%, respectively, correspond to an optimal cut-off of 87 μg/L. Receiver operating characteristics curve analysis revealed that ELISA analysis of hepcidin is not superior to ferritin in the diagnosis of iron deficiency in elderly anaemic patients with concurrent inflammation. Hepcidin shows a strong positive correlation with ferritin, and also correlates positively with C-reactive protein in this patient population.
Literature
1.
go back to reference Merchant A, Roy C. Not so benign haematology: anaemia of the elderly. Br J Haematol. 2012;156:173–85.CrossRefPubMed Merchant A, Roy C. Not so benign haematology: anaemia of the elderly. Br J Haematol. 2012;156:173–85.CrossRefPubMed
2.
go back to reference Wessling-Resnick M. Iron homeostasis and inflammatory response. Ann Rev Nutr. 2010;30:105–22.CrossRef Wessling-Resnick M. Iron homeostasis and inflammatory response. Ann Rev Nutr. 2010;30:105–22.CrossRef
3.
go back to reference Clark S. Iron deficiency anemia: diagnosis and management. Curr Opin Gastroenterol. 2009;25:122–8.CrossRefPubMed Clark S. Iron deficiency anemia: diagnosis and management. Curr Opin Gastroenterol. 2009;25:122–8.CrossRefPubMed
4.
go back to reference Phiri K, Calis J, Kachala D, Borgstein E, Waluza J, Bates I, et al. Improved method for assessing iron stores in the bone marrow. J Clin Pathol. 2009;62:685–9.CrossRefPubMedPubMedCentral Phiri K, Calis J, Kachala D, Borgstein E, Waluza J, Bates I, et al. Improved method for assessing iron stores in the bone marrow. J Clin Pathol. 2009;62:685–9.CrossRefPubMedPubMedCentral
7.
go back to reference Kemna E, Tjalsma H, Laarakkers C, Nemeth E, Willems H, Swinkels D. Novel urine hepcidin assay by mass spectrometry. Blood. 2005;106:3268–70.CrossRefPubMed Kemna E, Tjalsma H, Laarakkers C, Nemeth E, Willems H, Swinkels D. Novel urine hepcidin assay by mass spectrometry. Blood. 2005;106:3268–70.CrossRefPubMed
8.
go back to reference Kemna E, Tjalsma H, Podust V, Swinkels D. Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem. 2007;53:620–8.CrossRefPubMed Kemna E, Tjalsma H, Podust V, Swinkels D. Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem. 2007;53:620–8.CrossRefPubMed
9.
go back to reference Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M. Immunoassay for human hepcidin. Blood. 2008;112:4292–7.CrossRefPubMed Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M. Immunoassay for human hepcidin. Blood. 2008;112:4292–7.CrossRefPubMed
10.
go back to reference Karlsson T. Comparative evaluation of the reticulocyte hemoglobin content assay when screening for iron deficiency in elderly anemic patients. Anemia. 2011;2011:925907. Karlsson T. Comparative evaluation of the reticulocyte hemoglobin content assay when screening for iron deficiency in elderly anemic patients. Anemia. 2011;2011:925907.
11.
go back to reference Karlsson T. Mass spectrometry evaluation of the hepcidin-25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients. Eur J Haematol. 2015;95:467–71.CrossRefPubMed Karlsson T. Mass spectrometry evaluation of the hepcidin-25 assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients. Eur J Haematol. 2015;95:467–71.CrossRefPubMed
12.
go back to reference Guralnik J, Eisenstaedt R, Fellucci L, Klein H, Woodman R. Prevalence of anemia in persons 65 years or older in the unites states: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263–8.CrossRefPubMed Guralnik J, Eisenstaedt R, Fellucci L, Klein H, Woodman R. Prevalence of anemia in persons 65 years or older in the unites states: evidence for a high rate of unexplained anemia. Blood. 2004;104:2263–8.CrossRefPubMed
13.
15.
go back to reference Punnonen K, Irjala K, Rajamäki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood. 1997;89:1052–7.PubMed Punnonen K, Irjala K, Rajamäki A. Serum transferrin receptor and its ratio to serum ferritin in the diagnosis of iron deficiency. Blood. 1997;89:1052–7.PubMed
16.
go back to reference Thomas C, Thomas L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem. 2002;48:1066–77.PubMed Thomas C, Thomas L. Biochemical markers and hematologic indices in the diagnosis of functional iron deficiency. Clin Chem. 2002;48:1066–77.PubMed
17.
go back to reference Abitbol V, Borderie D, Polin V, Maksimovic F, Sarafati G, Esch A, et al. Diagnosis of iron deficiency in inflammatory bowel disease by transferrin receptor-ferritin index. Medicine. 2015;94:e1011.CrossRefPubMedPubMedCentral Abitbol V, Borderie D, Polin V, Maksimovic F, Sarafati G, Esch A, et al. Diagnosis of iron deficiency in inflammatory bowel disease by transferrin receptor-ferritin index. Medicine. 2015;94:e1011.CrossRefPubMedPubMedCentral
18.
go back to reference Chen YC, Hung SC, Tarng DC. Association between transferrin receptor-ferritin index and conventional measures of iron responsiveness in hemodialysis patients. Am J Kidney Dis. 2006;47:1036–44.CrossRefPubMed Chen YC, Hung SC, Tarng DC. Association between transferrin receptor-ferritin index and conventional measures of iron responsiveness in hemodialysis patients. Am J Kidney Dis. 2006;47:1036–44.CrossRefPubMed
19.
go back to reference Skikne B, Punnonen K, Caldron P, Bennett M, Rehu M, Gasior G, et al. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. Am J Hematol. 2011;86:923–7.CrossRefPubMed Skikne B, Punnonen K, Caldron P, Bennett M, Rehu M, Gasior G, et al. Improved differential diagnosis of anemia of chronic disease and iron deficiency anemia: a prospective multicenter evaluation of soluble transferrin receptor and the sTfR/log ferritin index. Am J Hematol. 2011;86:923–7.CrossRefPubMed
20.
go back to reference Kotru M, Rusia U, Sikka M, Chaturvedi S, Jain A. Evaluation of serum ferritin in screening for iron deficiency in tuberculosis. Ann Hematol. 2004;83:95–100.CrossRefPubMed Kotru M, Rusia U, Sikka M, Chaturvedi S, Jain A. Evaluation of serum ferritin in screening for iron deficiency in tuberculosis. Ann Hematol. 2004;83:95–100.CrossRefPubMed
21.
go back to reference Phatlhane D, Zemlin A, Matsha T, Hoffmann M, Naidoo N, Ichihara K, et al. The iron status of healthy south african population. Clin Chim Acta. 2016;460:240–5.CrossRefPubMed Phatlhane D, Zemlin A, Matsha T, Hoffmann M, Naidoo N, Ichihara K, et al. The iron status of healthy south african population. Clin Chim Acta. 2016;460:240–5.CrossRefPubMed
22.
go back to reference Chandyo R, Henjum S, Ulak M, Thorne-Lyman A, Ulvik R, Shretsa S, et al. The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal. Eur J Clin Nutr. 2016;70:456–62.CrossRefPubMed Chandyo R, Henjum S, Ulak M, Thorne-Lyman A, Ulvik R, Shretsa S, et al. The prevalence of anemia and iron deficiency is more common in breastfed infants than their mothers in Bhaktapur, Nepal. Eur J Clin Nutr. 2016;70:456–62.CrossRefPubMed
23.
go back to reference Genc S, Erten N, Karan M, Besisik S, Saka B, Tascioglu C, et al. Soluble transferrin receptor and soluble transferrin receptor-ferritin index for evaluation of the iron status in elderly patients. Tohuko J Exp Med. 2004;202:135–42.CrossRef Genc S, Erten N, Karan M, Besisik S, Saka B, Tascioglu C, et al. Soluble transferrin receptor and soluble transferrin receptor-ferritin index for evaluation of the iron status in elderly patients. Tohuko J Exp Med. 2004;202:135–42.CrossRef
24.
go back to reference Kroot J, Laarakkers C, Geurts-Mosepot A, Grebenchtchikov N, Pickkers P, van Ede A, et al. Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism. Clin Chem. 2010;56:1570–9.CrossRefPubMed Kroot J, Laarakkers C, Geurts-Mosepot A, Grebenchtchikov N, Pickkers P, van Ede A, et al. Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism. Clin Chem. 2010;56:1570–9.CrossRefPubMed
25.
go back to reference Van Santen S, Dongen-Lases E, de Vegt F, Laarakkers C, van Riel P, van Ede A, et al. Hepcidin and hemoglobin content parameters in the diagnosis of iron deficiency in rheumatoid arthritis patients with anemia. Arthritis Rheum. 2011;63:3672–80.CrossRefPubMed Van Santen S, Dongen-Lases E, de Vegt F, Laarakkers C, van Riel P, van Ede A, et al. Hepcidin and hemoglobin content parameters in the diagnosis of iron deficiency in rheumatoid arthritis patients with anemia. Arthritis Rheum. 2011;63:3672–80.CrossRefPubMed
26.
go back to reference Butterfield A, Luan P, Witcher D, Manetta J, Murphy A, Wroblewski V, et al. A dual-monoclonal sandwich ELISA specific for hepcidin-25. Clin Chem. 2010;56:1725–32.CrossRefPubMed Butterfield A, Luan P, Witcher D, Manetta J, Murphy A, Wroblewski V, et al. A dual-monoclonal sandwich ELISA specific for hepcidin-25. Clin Chem. 2010;56:1725–32.CrossRefPubMed
27.
go back to reference Dahlfors G, Stål P, Hansson E, Barany P, Sisowath C, Onelöv L, et al. Validation of a competitive ELISA assay for the quantification of human serum hepcidin. Scand J Clin Lab Invest. 2015;75:1–7.CrossRef Dahlfors G, Stål P, Hansson E, Barany P, Sisowath C, Onelöv L, et al. Validation of a competitive ELISA assay for the quantification of human serum hepcidin. Scand J Clin Lab Invest. 2015;75:1–7.CrossRef
28.
go back to reference Geerts I, Vermeersch P, Joosten E. Evaluation of the first commercial hepcidin ELISA for the differential diagnosis of anemia of chronic disease and iron deficiency anemia in hospitalized geriatric patients. ISRN Hematol. 2012;2012:567941. Geerts I, Vermeersch P, Joosten E. Evaluation of the first commercial hepcidin ELISA for the differential diagnosis of anemia of chronic disease and iron deficiency anemia in hospitalized geriatric patients. ISRN Hematol. 2012;2012:567941.
29.
go back to reference Cheng P-P, Jiao X-Y, Wang X-H, Lin J-H, Cai Y-M. Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia. Clin Exp Med. 2011;11:33–42.CrossRefPubMed Cheng P-P, Jiao X-Y, Wang X-H, Lin J-H, Cai Y-M. Hepcidin expression in anemia of chronic disease and concomitant iron-deficiency anemia. Clin Exp Med. 2011;11:33–42.CrossRefPubMed
30.
go back to reference Shu T, Jing C, Lv Z, Xie Y, Xu J, Wu J. Hepcidin in tumor-related iron deficiency anemia and tumor-related anemia of chronic disease: pathogenic mechanisms and diagnosis. Eur J Haematol. 2014;94:67–73.CrossRefPubMed Shu T, Jing C, Lv Z, Xie Y, Xu J, Wu J. Hepcidin in tumor-related iron deficiency anemia and tumor-related anemia of chronic disease: pathogenic mechanisms and diagnosis. Eur J Haematol. 2014;94:67–73.CrossRefPubMed
31.
go back to reference Barsan L, Stanciu A, Stancu S, Capusa C, Bratescu L, Mandache E, et al. Bone marrow iron distribution, hepcidin, and ferroportin expression in renal anemia. Hematology. 2015;20:543–52.CrossRefPubMed Barsan L, Stanciu A, Stancu S, Capusa C, Bratescu L, Mandache E, et al. Bone marrow iron distribution, hepcidin, and ferroportin expression in renal anemia. Hematology. 2015;20:543–52.CrossRefPubMed
32.
go back to reference Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen B, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulating hormone hepcidin. J Clin Invest. 2004;113:1271–6.CrossRefPubMedPubMedCentral Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen B, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulating hormone hepcidin. J Clin Invest. 2004;113:1271–6.CrossRefPubMedPubMedCentral
33.
go back to reference Kattamis A, Papassotiriou I, Palaiologou D, Apostolakou F, Galani A, Ladis V, et al. The effect on erythropoietic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica. 2006;91:809–12.PubMed Kattamis A, Papassotiriou I, Palaiologou D, Apostolakou F, Galani A, Ladis V, et al. The effect on erythropoietic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica. 2006;91:809–12.PubMed
34.
Metadata
Title
Evaluation of a competitive hepcidin ELISA assay in the differential diagnosis of iron deficiency anaemia with concurrent inflammation and anaemia of inflammation in elderly patients
Author
Torbjörn Karlsson
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2017
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/s12950-017-0166-3

Other articles of this Issue 1/2017

Journal of Inflammation 1/2017 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.