Abstract
Non-Tf-bound iron (NTBI), which appears in serum in iron overload, is thought to contribute to organ damage; the monitoring of serum NTBI levels may therefore be clinically useful in iron-overloaded patients. However, NTBI quantification methods remain complex, limiting their use in clinical practice. To overcome the technical difficulties often encountered, we recently developed a novel automated NTBI quantification system capable of measuring large numbers of samples. In the present study, we investigated the in vivo behavior of NTBI in human and animal serum using this newly established automated system. Average NTBI in healthy volunteers was 0.44 ± 0.076 μM (median 0.45 μM, range 0.28–0.66 μM), with no significant difference between sexes. Additionally, serum NTBI rapidly increased after iron loading, followed by a sudden disappearance. NTBI levels also decreased in inflammation. The results indicate that NTBI is a unique marker of iron metabolism, unlike other markers of iron metabolism, such as serum ferritin. Our new automated NTBI quantification method may help to reveal the clinical significance of NTBI and contribute to our understanding of iron overload.
References
Kwiatkowski JL. Management of transfusional iron overload-differential properties and efficacy of iron chelating agents. J Blood Med. 2011;2:135–49.
Brissot P, Ropert M, Le Lan C, Loréal O. Non-transferrin bound iron: a key role in iron overload and iron toxicity. Biochim Biophys Acta. 2012;1820:403–10.
Taher AT, Musallam KM, Inati A. Iron overload. Consequences, assessment, and monitoring. Hemoglobin. 2009;33(Suppl 1):S46–57.
Belotti A, Duca L, Borin L, et al. Non transferrin bound iron (NTBI) in acute leukemias throughout conventional intensive chemotherapy: kinetics of its appearance and potential predictive role in infections complications. Leuk Res. 2015;39:88–91.
Prakash M, Upadhya S, Prabhu R. Serum non-transferrin bound iron in hemodialysis patients not receiving intravenous iron. Clin Chim Acta. 2005;360:194–8.
Malyszko J, Koc-Zorawska E, Levin-Iaina N, et al. Iron metabolism in hemodialyzed patients—a story half told? Arch Med Sci. 2014;10:1117–22.
List AF, Baer MR, Steensma DP, et al. Deferasirox reduces serum ferritin and labile plasma iron in RBC transfusion-dependent patients with myelodysplastic syndrome. J Clin Oncol. 2012;30:2134–9.
Cortelezzi A, Cattaneo C, Cristiani S, et al. Non-transferrin-bound iron in myelodysplastic syndromes: a marker of ineffective erythropoiesis? Hematol J. 2000;1:153–8.
Goto T, Ikuta K, Inamoto Y, et al. Hyperferritinemia after adult allogeneic hematopoetic cell transplantation: quantification of iron burden by determining non-transferrin-bound iron. Int J Hematol. 2013;97:125–34.
Le Lan C, Loréal O, Cohen T, et al. Redox active plasma iron in C282Y/C282Y hemochromatosis. Blood. 2005;105:4527–31.
Breuer W, Hershko C, Cabantchik ZI. The importance of non-transferrin bound iron in disorders of iron metabolism. Transfus Sci. 2000;23:185–92.
Ito S, Ikuta K, Kato D, et al. Non-transferrin-bound iron assay system utilizing a conventional automated analyzer. Clin Chim Acta. 2014;437:129–35.
Sasaki K, Ikuta K, Tanaka H, et al. Improved quantification for non-transferrin-bound iron measurement using high-performance liquid chromatography by reducing iron contamination. Mol Med Rep. 2011;4:913–8.
Kroot JJ, Tjalsma H, Fleming RE, Swinkels DW. Hepcidin in human iron disorders: diagnostic implications. Clin Chem. 2011;57:1650–69.
Sasaki Y, Shimonaka Y, Ikuta K, et al. Hepcidin production in response to iron is controlled by monocyte-derived humoral factors. Int J Hematol. 2014;99:12–20.
Nemeth E, Ganz T. Anemia of inflammation. Hematol Oncol Clin North Am. 2014;28:671–81.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
Satoshi Ito, Katsuya Ikuta, Lynda Addo, Kotoe Shibusa, Yasumichi Toki, Mayumi Hatayama, Masayo Yamamoto, Motohiro Shindo, Yutaka Kohgo, Mikihiro Fujiya (Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical University and Department of Gastrointestinal Immunology and Regenerative Medicine, Asahikawa Medical University) received research funding from Shino-Test Corporation; this study was also performed in collaboration with Shino-Test Corporation. The above-mentioned departments also received collaborative research funding from Novartis Pharma K.K., Asahi Kasei Medical Co. Ltd., and Chugai Pharmaceutical Co. Ltd. for iron metabolism research work.
About this article
Cite this article
Ito, S., Ikuta, K., Kato, D. et al. In vivo behavior of NTBI revealed by automated quantification system. Int J Hematol 104, 175–181 (2016). https://doi.org/10.1007/s12185-016-2002-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12185-016-2002-6