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Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case–control study

Abstract

Recently, hepcidin, an antimicrobial-like peptide hormone, has evolved as the master regulator of systemic iron homeostasis. Hepcidin integrates signals from diverse physiological inputs, forming a key connection between iron trafficking and response to infection. In this study, we aimed to investigate whether Helicobacter pylori infection modulates serum hepcidin level and response to oral iron therapy in children with iron-deficiency anemia. This was a case–control study including 60 children with iron-deficiency anemia (IDA; 30 H. pylori infected and 30 H. pylori noninfected) and 30 healthy children with comparable age and gender as the control group. Iron parameters including serum iron, ferritin, transferrin, total iron binding capacity, and transferrin saturation and serum hepcidin levels were assessed initially and after 3 months of oral iron therapy for IDA. Compared to the control group, serum hepcidin was significantly lower in H. pylori-noninfected children with IDA (P < 0.01) and significantly higher in H. pylori-infected children with IDA (P < 0.01). Hepcidin increased significantly in noninfected children with IDA after 3 months of oral iron therapy (P < 0.01). On the other hand, H. pylori-infected children showed nonsignificant change in hepcidin level after oral iron therapy (P > 0.05). Although hepcidin showed significant positive correlations with serum ferritin, hemoglobin (Hb), iron, and transferrin saturation in noninfected children with IDA (P < 0.01), it showed significant negative correlations with serum ferritin, Hb, iron, and transferrin saturation in H. pylori-infected children with IDA (P < 0.05). H. pylori infection upregulates serum hepcidin levels and was associated with diminished response to oral iron therapy in children with iron-deficiency anemia.

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References

  1. Kato S, Sherman PM (2005) What is new related to Helicobacter pylori infection in children and teenagers? Arch Pediatr Adolesc Med 159(5):415–21

    PubMed  Article  Google Scholar 

  2. Weyermann M, Rothenbacher D, Brenner H (2009) Acquisition of Helicobacter pylori infection in early childhood: independent contributions of infected mothers, fathers, and siblings. Am J Gastroenterol 104:182–189

    PubMed  Article  Google Scholar 

  3. Ge R, Sun X (2012) Iron trafficking system in Helicobacter pylori. Biometals 25(2):247–58

    PubMed  Article  CAS  Google Scholar 

  4. United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition and International Food Policy Research Institute (2000) Fourth Report of the World Nutrition Situation. Geneva, Switzerland: United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition

  5. Lozoff B, Jimenez E, Smith JB (2006) Double burden of iron deficiency in infancy and low socioeconomic status: a longitudinal analysis of cognitive test scores to age 19 years. Arch Pediatr Adolesc Med 160(11):1108–1113

    PubMed  Article  Google Scholar 

  6. Muhsen K, Cohen D (2008) Helicobacter pylori infection and iron stores: a systematic review and meta-analysis. Helicobacter 13:323–40

    PubMed  Article  CAS  Google Scholar 

  7. Lee SY, Song EY, Yun YM, Yoon SY, Cho YH, Kim SY, Lee MH (2010) Serum prohepcidin levels in Helicobacter pylori infected patients with iron deficiency anemia. Korean J Intern Med 25(2):195–200

    PubMed  Article  CAS  Google Scholar 

  8. Pellicano R, Rizzetto M (2004) Is hepcidin the bridge linking Helicobacter pylori and anaemia of chronic infection? A research proposal. Panminerva Med 46:165–169

    PubMed  CAS  Google Scholar 

  9. Ganz T (2003) Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood 102:783–788

    PubMed  Article  CAS  Google Scholar 

  10. Kemna EH, Tjalsma H, Willems HL, Swinkels DW (2008) Hepcidin: from discovery to differential diagnosis. Haematologica 93:90–97

    PubMed  Article  CAS  Google Scholar 

  11. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306(5704):2090–2093

    PubMed  Article  CAS  Google Scholar 

  12. Kroot JJ, Tjalsma H, Fleming RE, Swinkels DW (2011) Hepcidin in human iron disorders: diagnostic implications. Clin Chem 57(12):1650–69

    PubMed  Article  CAS  Google Scholar 

  13. Cherian S, Forbes DA, Cook AG, Sanfilippo FM, Kemna EH, Swinkels DW, Burgner DP (2008) An insight into the relationships between hepcidin, anemia, infections and inflammatory cytokines in pediatric refugees: a cross-sectional study. PLoS One 3(12):e4030

    PubMed  Article  Google Scholar 

  14. Zimmermann MB, Hurrell RF (2007) Nutritional iron deficiency. Lancet 370:511–520

    PubMed  Article  CAS  Google Scholar 

  15. Cherian S, Burgner D, Carson C, Sanfilippo F, Cook A et al (2008) Diagnosis of Helicobacter pylori infection in a high prevalence pediatric population: a comparison of 2 fecal antigen testing methods and serology. J Pediatr Gastroenterol Nutr 47:130–135

    PubMed  Article  Google Scholar 

  16. Kroot JJ, Hendriks JC, Laarakkers CM, Klaver SM, Kemna EH et al (2009) (Pre)analytical imprecision, between-subject variability, and daily variations in serum and urine hepcidin: implications for clinical studies. Anal Biochem 389:124–129

    PubMed  Article  CAS  Google Scholar 

  17. Brătescu LO, Bârsan L, Munteanu D, Stancu S, Mircescu G (2010) Is hepcidin-25 a clinically relevant parameter for the iron status in hemodialysis patients? J Ren Nutr 20(5Suppl):S77–S83

    PubMed  Article  Google Scholar 

  18. Qu XH, Huang XL, Xiong P, Zhu CY, Huang YL et al (2010) Does Helicobacter pylori infection play a role in iron deficiency anemia? A meta-analysis. World J Gastroenterol 16:886–896

    PubMed  CAS  Google Scholar 

  19. Cardenas VM, Mulla ZD, Ortiz M, Graham DY (2006) Iron deficiency and Helicobacter pylori infection in the United States. Am J Epidemiol 163:127–134

    PubMed  Article  Google Scholar 

  20. Zamani A, Shariat M, Oloomi Yazdi Z, Bahremand S, Akbari Asbagh P, Dejakam A (2011) Relationship between Helicobacter pylori infection and serum ferritin level in primary school children in Tehran-Iran. Acta Med Iran 49(5):314–8

    PubMed  Google Scholar 

  21. World Health Organization, United Nations Children’s Fund. University UN (2001) Iron deficiency anaemia: assessment, prevention and control. World Health Organization, Geneva, pp 1–132

    Google Scholar 

  22. Drakesmith H, Prentice AM (2012) Hepcidin and the iron-infection axis. Science 338(6108):768–72

    PubMed  Article  CAS  Google Scholar 

  23. Marguti I (2012) Control of immunopathology during Plasmodium infection by hepcidin. Med Hypotheses 78:250–253

    PubMed  Article  CAS  Google Scholar 

  24. Beutler E (2007) Hepcidin mimetics from microorganisms? A possible explanation for the effect of Helicobacter pylori on iron homeostasis. Blood Cells Mol Dis 38:54–55

    PubMed  Article  CAS  Google Scholar 

  25. Johnson EE, Wessling-Resnick M (2012) Iron metabolism and the innate immune response to infection. Microbes Infect 14(3):207–16

    PubMed  Article  CAS  Google Scholar 

  26. Nemeth E, Ganz T (2009) The role of hepcidin in iron metabolism. Acta Haematol 122(2–3):78–86

    PubMed  Article  CAS  Google Scholar 

  27. Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111(12):1805–12

    PubMed  CAS  Google Scholar 

  28. Elalfy MS, Hamdy AM, Maksoud SS, Megeed RI (2012) Pattern of milk feeding and family size as risk factors for iron deficiency anemia among poor Egyptian infants 6 to 24 months old. Nutr Res 32(2):93–9

    PubMed  Article  CAS  Google Scholar 

  29. Zhang ZF, Yang N, Zhao G, Zhu L, Zhu Y, Wang LX (2010) Effect of Helicobacter pylori eradication on iron deficiency. Chin Med J (Engl) 123(14):1924–30

    CAS  Google Scholar 

  30. Xia W, Zhang X, Wang J, Sun C, Wu L (2012) Survey of anaemia and Helicobacter pylori infection in adolescent girls in Suihua, China and enhancement of iron intervention effects by H. pylori eradication. Br J Nutr 108(2):357–62

    PubMed  Article  CAS  Google Scholar 

  31. Choe YH, Kim SK, Son BK, Lee DH, Hong YC, Pai SH (1999) Randomized placebo-controlled trial of Helicobacter pylori eradication for iron-deficiency anemia in preadolescent children and adolescents. Helicobacter 4:135–139

    PubMed  Article  CAS  Google Scholar 

  32. Sarker SA, Mahmud H, Davidsson L, Alam NH, Ahmed T, Alam N, Salam MA, Beglinger C, Gyr N, Fuchs GJ (2008) Causal relationship of Helicobacter pylori with iron-deficiency anemia or failure of iron supplementation in children. Gastroenteroloy 135(5):1534–42

    Article  CAS  Google Scholar 

  33. Dogan A, Alioglu B, Dindar N, Dallar Y (2013) Increased serum hepcidin and ghrelin levels in children treated for iron deficiency anemia. J Clin Lab Anal 27(1):81–5

    PubMed  Article  CAS  Google Scholar 

  34. Eisenbarth SC, Flavell RA (2009) Innate instruction of adaptive immunity revisited: the inflammasome. EMBO Mol Med 1:92–98

    PubMed  Article  CAS  Google Scholar 

  35. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, Ganz T (2004) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276

    PubMed  CAS  Google Scholar 

  36. De Domenico I, Zhang TY, Koening CL, Branch RW, London N, Lo E, Daynes RA, Kushner JP, Li D, Ward DM, Kaplan J (2010) Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest 120:2395–2405

    PubMed  Article  Google Scholar 

  37. Choi HS, Song SH, Lee JH, Kim HJ, Yang HR (2012) Serum hepcidin levels and iron parameters in children with iron deficiency. Korean J Hematol 47(4):286–92

    PubMed  Article  CAS  Google Scholar 

  38. Rehu M, Punnonen K, Ostland V, Heinonen S, Westerman M, Pulkki K, Sankilampi U (2010) Maternal serum hepcidin is low at term and independent of cord blood iron status. Eur J Haematol 85:345–352

    PubMed  Article  CAS  Google Scholar 

  39. Ganz T (2011) Hepcidin and iron regulation, 10 years later. Blood 117:4425–4433

    PubMed  Article  CAS  Google Scholar 

  40. Roe M, Collings R, Dainty JR, Swinkels DW, Fairweather-Tait SJ (2009) Plasma hepcidin concentrations significantly predict interindividual variation in iron absorption in healthy men. Am J Clin Nutr 89:1088–91

    PubMed  Article  CAS  Google Scholar 

  41. Young MF, Glahn RP, Riza-Nieto M, Inglis J, Olbina G, Westerman M, O’Brien KO (2009) Serum hepcidin is significantly associated with iron absorption from food and supplemental sources in healthy young women. Am J Clin Nutr 89:533–538

    PubMed  Article  CAS  Google Scholar 

  42. Zimmermann MB, Troesch B, Biebinger R, Egli I, Zeder C, Hurrell RF (2009) Plasma hepcidin is a modest predictor of dietary iron bioavailability in humans, whereas oral iron loading, measured by stable-isotope appearance curves, increases plasma hepcidin. Am J Clin Nutr 90:1280–7

    PubMed  Article  CAS  Google Scholar 

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Acknowledgments

The authors would like to thank Dr. Mona Abo Serea for her statistical assistance. The authors also thank the staff of outpatient clinics in Zagazig University Children’s Hospital for their collaboration in sampling as well as our patients who participated in the study. Our institutional review committee of ethical research approved the study.

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The authors declare that they have no conflict of interest.

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Correspondence to Seham F. A. Azab.

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Azab, S.F.A., Esh, A.M.H. Serum hepcidin levels in Helicobacter pylori-infected children with iron-deficiency anemia: a case–control study. Ann Hematol 92, 1477–1483 (2013). https://doi.org/10.1007/s00277-013-1813-2

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  • DOI: https://doi.org/10.1007/s00277-013-1813-2

Keywords

  • Hepcidin
  • Iron deficiency
  • Anemia
  • Helicobacter pylori
  • Children