Biomedical papers, 2016 (vol. 160), issue 2

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016, 160(2):231-237 | 10.5507/bp.2015.054

Characterization of iron metabolism and erythropoiesis in erythrocyte membrane defects and thalassemia traits

Lucie Sulovskaa, Dusan Holubb, Zuzana Zidovac, Martina Divokad, Marian Hajduchb, Vladimir Mihala, Jana Vrbkovab, Monika Horvathovac, Dagmar Pospisilovaa
a Department of Pediatrics, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic
b Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
c Department of Biology, Faculty of Medicine and Dentistry, Palacky University Olomouc, Czech Republic
d Department of Hemato-oncology, Faculty of Medicine and Dentistry, Palacky University Olomouc and University Hospital Olomouc, Czech Republic

Background and Aims: Erythropoiesis is closely related to iron metabolism in a balanced homeostasis. Analyses of diverse erythroid and iron metabolism disorders have shown that disrupted erythropoiesis negatively affects iron homeostasis and vice versa. The aim of this study was to characterize the relationship between erythropoietic activity and iron homeostasis in pediatric patients with erythrocyte membrane defects and thalassemia traits.

Methods: Selected markers of erythropoietic activity (erythropoietin, soluble transferrin receptor - sTfR and growth differentiation factor 15) and iron status parameters (serum iron, ferritin and hepcidin) were evaluated in pediatric patients with erythrocyte membrane defects and thalassemia traits.

Results: The patients with erythrocyte membrane defects and thalassemia traits had altered iron homeostasis due to disturbed erythropoiesis. In comparison with healthy controls, they had a normal to low hepcidin/ferritin ratio and concomitantly elevated sTfR.

Conclusion: The findings suggest that pediatric patients with erythrocyte membrane defects and thalassemia traits are more susceptible to iron overload than the general population and that the (hepcidin/ferritin)/sTfR ratio can be used to monitor any worsening of the disease.

Keywords: hepcidin, erythropoietic activity, erythrocyte membrane defects, thalassemia trait

Received: June 15, 2015; Accepted: October 16, 2015; Prepublished online: October 27, 2015; Published: June 24, 2016


References

  1. Weatherall DJ. Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias. Nat Rev Genet 2001;2(4):245-55. Go to original source... Go to PubMed...
  2. Piel FB, Weatherall DJ. The α-thalassemias. N Engl J Med 2014;371(20):1908-16. Go to original source... Go to PubMed...
  3. An X, Mohandas N. Disorders of red cell membrane. Br J Haematol 2008;141(3):367-75. Go to original source... Go to PubMed...
  4. Ganz T. Hepcidin in iron metabolism. Curr Opin Hematol 2004;11:251-4. Go to original source... Go to PubMed...
  5. Ganz T and Nemeth E. Hepcidin and disorders of iron metabolism. Annu Rev Med 2011;62:347-60. Go to original source... Go to PubMed...
  6. Tanno T, Bhanu NV, Oneal PA, Goh SH, Staker P, Lee YT, Moroney JW, Reed CH, Luban NL, Wang RH, Eling TE, Childs R, Ganz T, Leitman SF, Fucharoen S, Miller JL. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med 2007;13(9):1096-101. Go to original source... Go to PubMed...
  7. Tanno T, Miller JL. Iron loading and overloading due to ineffective erythropoiesis. Adv Hematol 2010;2010:358283. Go to original source... Go to PubMed...
  8. Kautz L, Jung G, Valore EV, Rivella S, Nemeth E, Ganz T. Identification of erythroferrone as an erythroid regulator of iron metabolism. Nat Genet 2014;46(7):678-84. Go to original source... Go to PubMed...
  9. Finch C. Regulators of iron balance in humans. Blood 1994;84(6):1697-702. Go to PubMed...
  10. Nemeth E. Hepcidin in beta-thalassemia. Ann N Y Acad Sci 2010;1202:31-5. Go to original source... Go to PubMed...
  11. Shalev H, Perez-Avraham G, Kapelushnik J, Levi I, Rabinovich A, Swinkels DW, Brasse-Lagnel C, Tamary H. High levels of soluble serum hemojuvelin in patients with congenital dyserythropoietic anemia type I. Eur J Haematol 2013;90(1):31-6. Go to original source... Go to PubMed...
  12. Mojzikova R, Koralkova P, Holub D, Zidova Z, Pospisilova D, Cermak J, Striezencova Laluhova Z, Indrak K, Sukova M, Partschova M, Kucerova J, Horvathova M, Divoky V. Iron status in patients with pyruvate kinase deficiency: neonatal hyperferritinaemia associated with a novel frameshift deletion in the PKLR gene (p.Arg518fs), and low hepcidin to ferritin ratios. Br J Haematol 2014;165(4):556-63. Go to original source... Go to PubMed...
  13. Pospisilova D, Holub D, Zidova Z, Sulovska L, Houda J, Mihal V, Hadacova I, Radova L, Dzubak P, Hajduch M, Divoky V, Horvathova M. Hepcidin levels in Diamond-Blackfan anemia reflect erythropoietic activity and transfusion dependency. Haematologica 2014;99(7):e118-21. Go to original source... Go to PubMed...
  14. Zadrazil J, Horak P, Horcicka V, Zahalkova J, Strebl P, Hruby M. Endogenous erythropoietin levels and anemia in long-term renal transplant recipients. Kidney and Blood Pressure Research 2007;30(2):108-16. Go to original source... Go to PubMed...
  15. Divoky V, Walczyskova S, Pospisilova D, Priwitzerova M, Takacova S, Kostelecka I, Divoka M, Rozmanova S, Jarosova M, Cermak J, Indrak K. [Rare forms of hereditary anaemia in the Czech and Slovak populations - β- and δβ-thalassaemia and unstable haemoglobin variants] Vnitr Lek 2005;51:886-93.
  16. Tanno T, Noel P, Miller JL. Growth differentiation factor 15 in erythroid health and disease. Curr Opin Hematol 2010;17(3):184-90. Go to original source... Go to PubMed...
  17. Ronzoni L, Sonzogni L, Duca L, Graziadei G, Cappellini MD, Ferru E. Growth Differentiation Factor 15 expression and regulation during erythroid differentiation in non-transfusion dependent thalassemia. Blood Cells Mol Dis 2015;54(1):26-8. Go to original source... Go to PubMed...
  18. Origa R, Galanello R, Ganz T, Giagu N, Maccioni L, Faa G, Nemeth E. Liver iron concentrations and urinary hepcidin in beta-thalassemia. Haematologica 2007;92(5):583-8. Go to original source... Go to PubMed...
  19. Pasricha SR, Frazer DM, Bowden DK, Anderson GJ. Transfusion suppresses erythropoiesis and increases hepcidin in adult patients with β-thalassemia major: a longitudinal study. Blood 2013;122(1):124-33. Go to original source... Go to PubMed...
  20. Guimarães JS, Cominal JG, Silva-Pinto AC, Olbina G, Ginzburg YZ, Nandi V, Westerman M, Rivella S, de Souza AM. Altered erythropoiesis and iron metabolism in carriers of thalassemia. Eur J Haematol 2015;94(6):511-8. Go to original source... Go to PubMed...
  21. Papanikolaou G, Tzilianos M, Christakis J, Bogdanos D, Tsimirika K, MacFarlane J, Goldberg YP, Sakellaropoulos N, Ganz T, Nemeth E. Hepcidin in iron overload disorders. Blood 2005;105(10):4103-5. Go to original source... Go to PubMed...
  22. Jones E, Pasricha SR, Allen A, Evans P, Fisher CA, Wray K, Premawardhena A, Bandara D, Perera A, Webster C, Sturges P, Olivieri NF, St Pierre T, Armitage AE, Porter JB, Weatherall DJ, Drakesmith H. Hepcidin is suppressed by erythropoiesis in hemoglobin E β-thalassemia and β-thalassemia trait. Blood 2015;125(5):873-80. Go to original source... Go to PubMed...
  23. Vokurka M, Krijt J, Sulc K, Necas E. Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol Res 2006;55(6):667-74. Go to PubMed...
  24. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood 2006;108(12):3730-5. Go to original source... Go to PubMed...