Skip to main content
SpringerLink
Log in

Hepcidin and Ferritin: Important Mediators in Inflammation Associated Anemia in Systemic Lupus Erythematosus Patients

  • Original Research Article
  • Published:
Indian Journal of Clinical Biochemistry Aims and scope Submit manuscript

Abstract

Systemic Lupus Erythematosus is an autoimmune disease with female preponderance. Anemia is found in 50% of Systemic Lupus Erythematosus patients. This is a cross sectional case control study with 30 female Systemic Lupus Erythematosus patients having inflammation associated anemia (Hemoglobin < 10.0 gm/dl) and 30 age matched controls with the aim to measure serum hepcidin and ferritin levels, correlate and study their role as homeostatic regulators of iron metabolism and utility as markers. Serum transferrin, ferritin, iron, total iron binding capacity, hsCRP, liver enzymes and renal parameters were analyzed by using automated analyser. Hepcidin levels were estimated by Sandwich-ELISA method. There was significant decrease in Iron (p < 0.0001), Iron Binding capacity (p < 0.0001), Transferrin (p < 0.0001) in patients, and a significant increase in inflammatory markers: hs-CRP (p < 0.0001), ESR (p < 0.0001) compared to controls. Significant increase in both Hepcidin (p < 0.0001) and Ferritin (p < 0.0001) was observed in patients with significant positive correlation (r = 0.711) with each other. Additionally, ferritin and hepcidin significantly positively correlated with hs-CRP and ESR (r = 0.526, 0.735); (r = 0.427, 0.742) respectively. Negative correlation with hemoglobin, iron, total iron binding capacity and transferrin with hepcidin (r = − 0.80, − 0.307, − 0.553, − 0.584) and ferritin (r = −0.722, − 0.22, − 0.654, − 0.728) was observed respectively. On ROC analysis both hepcidin and ferritin has sensitivity of 96.7%, specificity of 100% at cut-off values of 110 and 49 respectively. AUC of hepcidin was 0.993 and ferritin was 0.978. We have established a positive linear correlation between Hepcidin and Ferritin levels in disease activity and the changes correlated with the inflammatory state and anemia in patients, making them important mediators and potential markers of inflammation associated anemia.

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
Fig. 2

Similar content being viewed by others

References

  1. Laurence J, Wong JE, Nachman R. The cellular hematology of systemic lupus erythematosus. In: Lahita RG, editor. Systemic lupus erythematosus, vol. 100. 2nd ed. New York: Churchill Livingstone; 1992. p. 480.

    Google Scholar 

  2. Ramsey-Goldman R, Manzi S. Systemic lupus erythematosis. Women and health. Cambridge: Academic Press; 2000. p. 704.

    Google Scholar 

  3. Malaviya AN, Chandrasekaran AN, Kumar A, Sharma PN. Occasional series-lupus round the world: systemic lupus erythematosus in India. Lupus. 1997;6:690–700.

    Article  CAS  Google Scholar 

  4. Sasidharan PK. SLE as a hematological disease. In: Agarwal MB, editor. Hematolgy today. Mumbai: Vikas Publications; 2010. p. 953–66.

    Google Scholar 

  5. Liu H, Ozaki K, MatsuzakiY Abe M, Kosaka M, Saito S. Suppression of haematopoiesis by IgG autoantibodies from patients with systemic lupus erythematosus (SLE). Clin ExpImmunol. 1995;100(3):480–5.

    CAS  Google Scholar 

  6. Ludwiczek S, Aigner E, Theurl I, Weiss G. Cytokine-mediated regulation of iron transport in human monocytic cells. Blood. 2003;101:4148–54.

    Article  CAS  Google Scholar 

  7. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, Brissot P, Loréal O. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J Biol Chem. 2001;276:7811–9.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  9. Dupuy AM, Terrier N, Sénécal L, Morena M, Leray H, Canaud B, Cristol JP. Is C-reactive protein a marker of inflammation? Nephrologie. 2003;24(7):337–41.

    CAS  PubMed  Google Scholar 

  10. Hua B, Olsen EHN, Sun S, Gudme CN, Wang L, Vandahl B, Roepstorff K, Kjelgaard-Hansen M, Sørensen BB, Zhao Y, Karsdal MA, Manon-Jensen T. Serological biomarkers detect active joint destruction and inflammation in patients with haemophilicarthropathy. Haemophilia. 2017. doi:10.1111/hae.13196.

    Article  PubMed  Google Scholar 

  11. Zandman-Goddard G, Orbach H, Agmon-Levin N, Boaz M, Amital H, Szekanecz Z, Szucs G, Rovensky J, Kiss E, Corocher N, Doria A, Stojanovich L, Ingegnoli F, Meroni PL, Rozman B, Gomez-Arbesu J, Blank M, Shoenfeld Y. Hyperferritinemia is associated with serologic antiphospholipid syndrome in SLE patients. Clin Rev Allergy Immunol. 2013;44(1):23–30.

    Article  CAS  Google Scholar 

  12. Pradhan V, Pandit P, Rajadhyaksha A, Patwardhan M, Surve P, Kamble P, Lecerf M, Bayry J, Kaveri S, Ghosh K, Nadkar MY. Association of serum ferritin levels with hematological manifestations in systemic lupus erythematosus patients from Western India. J Assoc Physicians India. 2016;64(5):14–8.

    PubMed  Google Scholar 

  13. Nishiya K, Hashimoto K. Elevation of serum ferritin levels as a marker for active systemic lupus erythematosus. Clin Exp Rheumatol. 1997;15:39–44.

    CAS  PubMed  Google Scholar 

  14. Beyan E, Beyan C, Demirezer A, Ertugrul E, Uzuner A. The relationship between serum ferritin levels and disease activity in systemic lupus erythematosus. Scand J Rheumatol. 2003;32:225–8.

    Article  CAS  Google Scholar 

  15. Lim MK, Lee CK, Ju YS, Cho YS, Lee RS, Yoo B, Moon HB. Serum ferritin as a serologic marker of activity in systemic lupus erythematosus. Rheumatol Int. 2001;20:89–93.

    Article  CAS  Google Scholar 

  16. Dagli M, Yilmaz S, Sivrikaya A, Öztürk B. Role of prohepcidin andhepcidin in anemia associated with systemic lupus erythematosus. World Appl Sci J. 2011;13(9):2032–6.

    CAS  Google Scholar 

  17. HyeSung W, Hyun G, Yu S. IL-6 is an independent risk factor for resistance to erythropoiesis-stimulating agents in hemodialysis patients without iron deficiency. Hemodial Int. 2012;16:31–7.

    Article  Google Scholar 

  18. Umare V, Nadkarni A, Nadkar M, Rajadhyksha A, Khadilkar P, Ghosh K, Pradhan VD. Do high sensitivity C-reactive protein and serum interleukin-6 levels correlate with disease activity in systemic lupus erythematosuspatients? J Postgrad Med. 2017;63(2):92–5.

    Article  CAS  Google Scholar 

  19. Lee P, Peng H, Gelbart T, Wang L, Beutler E. Regulation of hepcidin transcription by interleukin-1 and interleukin-6. Proc Natl Acad Sci. 2005;102:1906–10.

    Article  CAS  Google Scholar 

  20. Roy CN, Andrews NC. Anemia of inflammation: the hepcidin link. Curr Opin Hematol. 2005;12(2):107–11.

    Article  CAS  Google Scholar 

  21. Mok CC, Birmingham D, Ho LY, Hebert L, Rovin B. THU0302. Hepcidin, Interleukin-6 and Anemia of Chronic Inflammation in Systemic Lupus Erythematosus (SLE). Ann Rheum Dis. 2013;72:A268.

    Article  Google Scholar 

  22. Demirag MD, Haznedaroglu S, Sancak B, Konca C, Gulbahar O, Ozturk MA, Goker B. Circulating hepcidin in the crossroads of anemia and inflammation associated with rheumatoid arthritis. Inter Med. 2009;48(6):421–6.

    Article  Google Scholar 

  23. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acutephase protein. Blood. 2003;101:2461–3.

    Article  CAS  Google Scholar 

  24. Roe MA, Spinks C, Heath AL, Harvey LJ, Foxall R, Wimperis J, Wolf C, Fairweather-Tait SJ. Serum prohepcidin concentration: no association with iron absorption in healthy men; and no relationship with iron status in men carrying HFE mutations, hereditary haemochromatosis, patients undergoing phlebotomy treatment, or pregnant women. Br J Nutr. 2007;97(3):544–9.

    Article  CAS  Google Scholar 

  25. Chogle AR. Utility of serum ferritin levels in the differenciation of anemia in Systemic Lupus Erythematosus. JAPI. 2016;64(5):11–2.

    PubMed  Google Scholar 

  26. Vanarsa K, Ye Y, Han J, Xie C, Mohan C, Tianfu W. Inflammation associated anemia and ferritin as disease markers in SLE. Arthritis Res Ther. 2012;14:R182.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, 500082, India

    Neeraja Kunireddy, Rachel Jacob, Siraj Ahmed Khan, B. Yadagiri, K. S. S. Sai Baba & Iyyapu Krishna Mohan

  2. Department of Rheumatology, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, 500082, India

    I. Rajendra Vara Prasad

Authors
  1. Neeraja Kunireddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rachel Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Siraj Ahmed Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B. Yadagiri
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. S. S. Sai Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. I. Rajendra Vara Prasad
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Iyyapu Krishna Mohan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Iyyapu Krishna Mohan.

Ethics declarations

Conflict of interest

Neeraja Kunireddy, Rachel Jacob, Siraj Ahmed Khan, B. Yadagiri, K.S.S. Sai Baba, I. Rajendra Vara Prasad and Iyyapu Krishna Mohan declare that we have no conflict of interest.

Ethical Approval

The study was approved by the hospital Institutional Ethical Committee (EC/NIMS/1396/2013).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kunireddy, N., Jacob, R., Khan, S.A. et al. Hepcidin and Ferritin: Important Mediators in Inflammation Associated Anemia in Systemic Lupus Erythematosus Patients. Ind J Clin Biochem 33, 406–413 (2018). https://doi.org/10.1007/s12291-017-0702-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12291-017-0702-1

Keywords

Search

Navigation