www.fgks.org   »   [go: up one dir, main page]
Skip to main content
SpringerLink
Log in

An insight into the relationships between prohepcidin, iron deficiency anemia, and interleukin-6 values in pediatric Helicobacter pylori gastritis

  • Original Article
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

The link between Helicobacter pylori and iron deficiency (ID) or iron deficiency anemia (IDA) has been investigated recently. We suggested that IDA/ID associated with H. pylori infection might be mediated by inflammation-driven hepcidin production. Patients with complaints of recurrent abdominal pain and dyspepsia aged between 7–16 years were included in this study. Patients were divided into two groups according to H. pylori status in upper gastrointestinal endoscopy. Group I who had H. pylori gastritis (n = 50) received triple antibiotic therapy. Group II (n = 50) who had H. pylori-negative gastritis only received proton pump inhibitor. Thirty healthy children with the similar age and gender were included in the study as a control group. Complete blood count, serum iron levels, iron-binding capacity, ferritin levels, prohepcidin and interleukin-6 (IL-6) values were evaluated in all children at the first visit. Initial tests were repeated after H. pylori eradication. Initial levels of ferritin (p = 0.002), prohepcidin (p = 0.003), and IL-6 (p = 0.004) were found significantly lower in group I compared to group II and the control group. The mean prohepcidin level was lower in the anemic H. pylori-positive group than in non-anemic H. pylori-positive group; however, the difference was not statistically significant. While significant increases in hematocrit and mean corpuscular volume were observed, no significant difference was found in serum ferritin, prohepcidin, or IL-6 level after eradication treatment in H. pylori-positive group. Conclusion: H. pylori-induced gastritis appears to cause an increase in prohepcidin levels and a decrease in ferritin levels, supporting our hypothesis; but this relationship has not been proven.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

H. pylori :

Helicobacter pylori

IDA:

Iron deficiency anemia

IL-6:

Interleukin-6

LPS:

Lipopolysaccharides

MCV:

Mean corpuscular volume

SD:

Standard deviation

References

  1. Barabino A (2002) Helicobacter pylori-related iron deficiency anemia: a review. Helicobacter 7(2):71–75

    Article  CAS  PubMed  Google Scholar 

  2. Barabino A, Dufour C, Marino CE, Claudiani F, De Alessandri A (1999) Unexplained refractory iron-deficiency anemia associated with Helicobacter pylori gastric infection in children: further clinical evidence. J Pediatr Gastroenterol Nutr 28(1):116–119

    Article  CAS  PubMed  Google Scholar 

  3. Baysoy G, Ertem D, Ademoglu E, Kotiloglu E, Keskin S, Pehlivanoglu E (2004) Gastric histopathology, iron status and iron deficiency anemia in children with Helicobacter pylori infection. J Pediatr Gastroenterol Nutr 38(2):146–151

    Article  CAS  PubMed  Google Scholar 

  4. Beutler E (2007) Hepcidin mimetics from microorganisms? A possible explanation for the effect of Helicobacter pylori on iron homeostasis. Blood Cells Mol Dis 38(1):54–55, discussion 56

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  5. Bohr UR, Annibale B, Franceschi F, Roccarina D, Gasbarrini A (2007) Extragastric manifestations of Helicobacter pylori infection—other Helicobacters. Helicobacter 12(Suppl 1):45–53

    Article  CAS  PubMed  Google Scholar 

  6. Caliskan Y, Yelken B, Ozkok A, Gorgulu N, Yazici H, Telci A, Yildiz A (2012) Lower serum prohepcidin levels associated with lower iron and erythropoietin requirements in hemodialysis patients with chronic hepatitis C. BMC Nephrol 13:56

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Capurso G, Lahner E, Marcheggiano A, Caruana P, Carnuccio A, Bordi C, Delle Fave G, Annibale B (2001) Involvement of the corporal mucosa and related changes in gastric acid secretion characterize patients with iron deficiency anaemia associated with Helicobacter pylori infection. Aliment Pharmacol Ther 15(11):1753–1761

    Article  CAS  PubMed  Google Scholar 

  8. Cardenas VM, Mulla ZD, Ortiz M, Graham DY (2006) Iron deficiency and Helicobacter pylori infection in the United States. Am J Epidemiol 163(2):127–134

    Article  PubMed  Google Scholar 

  9. 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

    Article  PubMed Central  PubMed  Google Scholar 

  10. Costa E, Swinkels DW, Laarakkers CM, Rocha-Pereira P, Rocha S, Reis F, Teixeira F, Miranda V, do Sameiro Faria M, Loureiro A, Quintanilha A, Belo L, Santos-Silva A (2009) Hepcidin serum levels and resistance to recombinant human erythropoietin therapy in haemodialysis patients. Acta Haematol 122(4):226–229

    Article  PubMed  Google Scholar 

  11. Dallalio G, Fleury T, Means RT (2003) Serum hepcidin in clinical specimens. Br J Haematol 122(6):996–1000

    Article  CAS  PubMed  Google Scholar 

  12. Dogan Y, Erkan T, Onal Z, Usta M, Dogusoy G, Cokugras FC, Kutlu T (2012) Lactoferrin levels in the gastric tissue of Helicobacter pylori-positive and -negative patients and its effect on anemia. Mediat Inflamm 2012:214581

    Article  Google Scholar 

  13. DuBois S, Kearney DJ (2005) Iron-deficiency anemia and Helicobacter pylori infection: a review of the evidence. Am J Gastroenterol 100(2):453–459

    Article  PubMed  Google Scholar 

  14. Figura N, Franceschi F, Santucci A, Bernardini G, Gasbarrini G, Gasbarrini A (2010) Extragastric manifestations of Helicobacter pylori infection. Helicobacter 15(Suppl 1):60–68

    Article  PubMed  Google Scholar 

  15. Ganz T, Nemeth E (2011) The hepcidin-ferroportin system as a therapeutic target in anemias and iron overload disorders. Hematology Am Soc Hematol Educ Program 2011:538–542

    Article  PubMed Central  PubMed  Google Scholar 

  16. Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M (2008) Immunoassay for human serum hepcidin. Blood 112(10):4292–4297

    Article  CAS  PubMed  Google Scholar 

  17. Ge R, Sun X (2012) Iron trafficking system in Helicobacter pylori. Biometals 25(2):247–258

    Article  CAS  PubMed  Google Scholar 

  18. Goddard AF, James MW, McIntyre AS, Scott BB (2011) Guidelines for the management of iron deficiency anaemia. Gut 60(10):1309–1316

    Article  CAS  PubMed  Google Scholar 

  19. Hershko C, Ronson A (2009) Iron deficiency, Helicobacter infection and gastritis. Acta Haematol 122(2–3):97–102

    Article  CAS  PubMed  Google Scholar 

  20. Kemna EH, Tjalsma H, Podust VN, Swinkels DW (2007) Mass spectrometry-based hepcidin measurements in serum and urine: analytical aspects and clinical implications. Clin Chem 53(4):620–628

    Article  CAS  PubMed  Google Scholar 

  21. Kulaksiz H, Gehrke SG, Janetzko A, Rost D, Bruckner T, Kallinowski B, Stremmel W (2004) Pro-hepcidin: expression and cell specific localisation in the liver and its regulation in hereditary haemochromatosis, chronic renal insufficiency, and renal anaemia. Gut 53(5):735–743

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. 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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Murphy AT, Witcher DR, Luan P, Wroblewski VJ (2007) Quantitation of hepcidin from human and mouse serum using liquid chromatography tandem mass spectrometry. Blood 110(3):1048–1054

    Article  CAS  PubMed  Google Scholar 

  24. Oustamanolakis P, Koutroubakis IE, Messaritakis I, Malliaraki N, Sfiridaki A, Kouroumalis EA (2011) Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease. Eur J Gastroenterol Hepatol 23(3):262–268

    Article  PubMed  Google Scholar 

  25. Ozkasap S, Yarali N, Isik P, Bay A, Kara A, Tunc B (2013) The role of prohepcidin in anemia due to Helicobacter pylori infection. Pediatr Hematol Oncol 30:425–431

    Article  CAS  PubMed  Google Scholar 

  26. Pacifico L, Anania C, Osborn JF, Ferraro F, Chiesa C (2010) Consequences of Helicobacter pylori infection in children. World J Gastroenterol 16(41):5181–5194

    Article  PubMed Central  PubMed  Google Scholar 

  27. Pellicano R, Rizzetto M (2004) Is hepcidin the bridge linking Helicobacter pylori and anemia of chronic infection? A research proposal. Panminerva Med 46(3):165–169

    CAS  PubMed  Google Scholar 

  28. Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, Walker LS (2006) Childhood functional gastrointestinal disorders: child/adolescent. Gastroenterology 130(5):1527–1537

    Article  PubMed  Google Scholar 

  29. Realdi G, Dore MP, Fastame L (1999) Extradigestive manifestations of Helicobacter pylori infection: fact and fiction. Dig Dis Sci 44(2):229–236

    Article  CAS  PubMed  Google Scholar 

  30. Sato Y, Yoneyama O, Azumaya M, Takeuchi M, Sasaki SY, Yokoyama J, Shioji K, Kawauchi Y, Hashimoto S, Nishigaki Y, Kobayashi M, Sugimura K, Honma T, Narisawa R, Aoyagi Y (2014) The relationship between iron deficiency in patients with Helicobacter pylori-infected nodular gastritis and the serum prohepcidin level. Helicobacter. doi:10.1111/hel.12170

    PubMed  Google Scholar 

  31. Schwarz P, Kubler JA, Strnad P, Muller K, Barth TF, Gerloff A, Feick P, Peyssonnaux C, Vaulont S, Adler G, Kulaksiz H (2012) Hepcidin is localised in gastric parietal cells, regulates acid secretion and is induced by Helicobacter pylori infection. Gut 61(2):193–201

    Article  CAS  PubMed  Google Scholar 

  32. Schwarz P, Strnad P, von Figura G, Janetzko A, Krayenbuhl P, Adler G, Kulaksiz H (2011) A novel monoclonal antibody immunoassay for the detection of human serum hepcidin. J Gastroenterol 46(5):648–656

    Article  CAS  PubMed  Google Scholar 

  33. Suzuki H, Franceschi F, Nishizawa T, Gasbarrini A (2011) Extragastric manifestations of Helicobacter pylori infection. Helicobacter 16(Suppl 1):65–69

    Article  PubMed  Google Scholar 

  34. Theil EC (2011) Iron homeostasis and nutritional iron deficiency. J Nutr 141(4):724S–728S

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Wilson DB (2009) Disorders of iron metabolism and sideroblastic anemia. In: Orkin SH, Nathan DG, Ginsburg D, Look AT, Fisher DE, Lux SE (eds) Nathan and Oski’s hematology of infancy and childhood, 7th edn. Saunders, Philadelphia, pp 522–542

    Google Scholar 

  36. 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):357–362

    Article  CAS  PubMed  Google Scholar 

  37. Young MF, Glahn RP, Ariza-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(2):533–538

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This project was granted by Gazi University (BAP 01/2010-69)

Conflicts of interest

The authors of this manuscript do not have any relevant financial disclosures and have no conflicts of interest to disclose regarding the content of this manuscript.

Author’s summary

In addition to the previously known causes of IDA, an association between H. pylori and pediatric IDA has been established in the past two decades. We suggested that IDA/ID associated with H. pylori infection might be mediated by inflammation-driven hepcidin production. H. pylori-induced gastritis appears to cause an increase in prohepcidin levels and a decrease in ferritin levels, supporting our hypothesis; but this relationship has not been proven.

There are only few studies in the literature evaluating the association between H. pylori infection, IDA, and hepcidin. Among these, only three studies were conducted in pediatric cases; and in one of them, cases with various infectious disorders were also included. Besides, in none of these studies, diagnosis of H. pylori infection was established histopathologically. Our study constitutes the first controlled study involving childhood cases, in which histopathological diagnostic procedures (considered to be the gold standard for diagnosis) were used.

Our study design is the most important factor setting it apart from previous researches. Previously proposed mechanisms do not resolve why IDA or iron deficiency develops in some, but not all, patients with H. pylori-induced gastritis. Thus, this study focused on H. pylori infection rather than anemia by conducting comparisons among patients with H. pylori-positive and H. pylori-negative gastritis and healthy individuals.

Author information

Authors and Affiliations

  1. Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

    Nagehan Emiralioglu

  2. Pediatric Hematology, Faculty of Medicine, Gazi University, Ankara, Turkey

    Idil Yenicesu

  3. Pediatric Gastroenterology, Faculty of Medicine, Gazi University, Ankara, Turkey

    Sinan Sari, Odul Egritas & Buket Dalgic

  4. Pathology, Faculty of Medicine, Gazi University, Ankara, Turkey

    Aylar Poyraz

  5. Biochemistry, Faculty of Medicine, Gazi University, Ankara, Turkey

    Ozge Tugce Pasaoglu

  6. Department of Biostatistics, Faculty of Health Sciences, Gazi University, Ankara, Turkey

    Bulent Celik

  7. Department of Pediatric Pulmonology, Faculty of Medicine, Hacettepe University, Sıhhiye, 06100, Ankara, Turkey

    Nagehan Emiralioglu

Authors
  1. Nagehan Emiralioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Idil Yenicesu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sinan Sari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Odul Egritas
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Aylar Poyraz
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ozge Tugce Pasaoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bulent Celik
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Buket Dalgic
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nagehan Emiralioglu.

Additional information

Communicated by David Nadal

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Emiralioglu, N., Yenicesu, I., Sari, S. et al. An insight into the relationships between prohepcidin, iron deficiency anemia, and interleukin-6 values in pediatric Helicobacter pylori gastritis. Eur J Pediatr 174, 903–910 (2015). https://doi.org/10.1007/s00431-014-2482-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-014-2482-4

Keywords

Search

Navigation