Correlations between Serum prohepcidin level disease activity in rheumatoid arthritis and systemic lupus erythematous



The aim of this study was to determine whether there is a relation between serum prohepcidin level and disease activity of rheumatoid arthritis (RA) and systemic lupus erythematous (SLE), and to discover whether it has a role in the anaemia of chronic disease occurring in RA and SLE patients.

Patients and methods

This study was carried out on 30 patients suffering from RA and 30 patients suffering from SLE. In addition, 20 healthy volunteers were recruited as controls. All patients and controls were subjected to full history taking, thorough clinical examination, locomotor system examination, assessment of the disease activity in RA patients using the Disease Activity Score-28, assessment of the disease activity in SLE patients using Systemic Lupus Erythematous Disease Activity Index, laboratory investigations, including complete blood count, erythrocyte sedimentation rate (ESR), rheumatoid factor and C-reactive protein (CRP), and measurement of serum prohepcidin levels by the enzyme-linked immunosorbant assay.


The mean serum prohepcidin concentration was 395.2±551.4ng/ml in RA patients, whereas it was 381.5±88.07 in SLE patients and 121.4±11.1ng/ml in healthy volunteers. The prohepcidin concentration correlated with the rheumatoid factor, Creactive protein, ESR, disease duration, morning stiffness, tender joint count, swollen joint count, Larsen score, haemoglobin level and Disease Activity Score-28 in RA patients. There were positive significant correlations between the mean serum prohepcidin concentration and platelets number, haemoglobin level and ESR in SLE patients and insignificant correlations between the mean serum prohepcidin concentration and Systemic Lupus Erythematous Disease Activity Index.


Prohepcidin could be considered as a useful marker for RA, but not for SLE. Prohepcidin may have a role in anaemia of chronic disease occurring in RA and SLE.


  1. 1

    Majithia V, Geraci SA. Rheumatoid arthritis: diagnosis and management. Am J Med 2007; 120:936–939.

    PubMed  Article  Google Scholar 

  2. 2

    Lu LJ, Wallace DJ, Ishimori ML, Scofield RH, Weisman MH. Male systemic lupus erythematosus: a review of sex disparities in this disease. Lupus 2010; 19:119–129.

    PubMed  Article  Google Scholar 

  3. 3

    Mehmet D, Sivrikya A, Celik G, Vatansev H. The role of prohepcidin and hepcidin in anemia associated with systemic lupus erythematous. World Appl Sci J 2011; 3:2032–2036.

    Google Scholar 

  4. 4

    Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 2002; 100:3376–3381.

    Article  Google Scholar 

  5. 5

    DemiragMD, Haznedaroglu S, Sancak B, Konca C, Gulbahar O, Ozturk MA, et al. Circulating hepcidin in the crossroads of anemia and inflammation associated with rheumatoid arthritis. Intern Med 2009; 48:421–426.

    PubMed  Article  Google Scholar 

  6. 6

    Oustamanolakis P, Koutroubakis IE, Messaritakis I, Malliaraki N, Sfiridaki A, Kouroumalis EA. Serum hepcidin and prohepcidin concentrations in inflammatory bowel disease. Eur JGastroenterolHepatol 2011; 23:262–268.

    Article  Google Scholar 

  7. 7

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

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. 8

    Ganz T. Hepcidin – a regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol 2005; 18:171–182.

    CAS  PubMed  Article  Google Scholar 

  9. 9

    Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheum 2010; 62:2569–2581.

    PubMed  Article  Google Scholar 

  10. 10

    Hochberg MC. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40:1725.

    CAS  PubMed  Article  Google Scholar 

  11. 11

    Aletaha D, Ward MM, Machold KP, Nell VPK, Stamm T, Smolen JS. Remission and active disease in rheumatoid arthritis: defining criteria for disease activity states. Arthritis Rheum 2005; 52:2625–2635.

    PubMed  Article  Google Scholar 

  12. 12

    Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. The Committee on Prognosis Studies in SLE. Derivation of the SLEDAI: a disease activity index for lupus patients. Arthritis Rheum 1992; 35:630–640.

    CAS  PubMed  Google Scholar 

  13. 13

    Rovetta G, Bianchi G, Monteforte P, Buffrini L, Ghirardo G. Automated diagnosis and characterization of Lyme disease using neutral network analysis. J Rheumatol 1995; 22:571–572.

    CAS  PubMed  Google Scholar 

  14. 14

    Tan EM. Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. Adv Immunol 1982; 33:167–239.

    CAS  PubMed  Article  Google Scholar 

  15. 15

    Roitt IM, Brostoff J, Male DK. Immunology. New York; London, Churchill Livingstone; Gower Medical Publishing 1985; 7.1–7.14.

    Google Scholar 

  16. 16

    Suragani RN, Cadena SM, Cawley SM, Sako D, Mitchell D, Li R, et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med 2014; 20:408–414.

    CAS  PubMed  Article  Google Scholar 

  17. 17

    Newman K, Owlia MB, El-Hemaidi I, Akhtari M. Management of immune cytopenias in patients with systemic lupus erythematosus – old and new. Autoimmun Rev 2013; 12:784–1784.

    PubMed  Article  Google Scholar 

  18. 18

    Theurl I, Schroll A, Nairz M, Seifert M, Theurl M, Sonnweber T, et al. Pathways for the regulation of hepcidin expression in anemia of chronic disease andiron deficiency anemia in vivo. Haematologica 2011; 96:1761–1769.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  19. 19

    Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood 2005; 106:2196–2199.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20

    Mecklenburg I, Reznik D, Fasler-Kan E, Beglinger C. Serum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease. J Crohns Colitis 2014; 8:1569–1752.

    Article  Google Scholar 

  21. 21

    Kemna E, Pickkers P, Nemeth E, Vander Hoeven H, Swinkels D. Timecourse analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood 2005; 106:1864–1866.

    CAS  PubMed  Article  Google Scholar 

  22. 22

    Dagli M, Yilmaz M, Sivrikaya A, Ozturk B. Serum prohepcidin and hepcidin levels in patients with ankylosing spondylitis: a prospective study. World Appl Sci J 2013; 28:1281–1285.

    CAS  Google Scholar 

  23. 23

    Paköz ZB, ÇekiçC, Arabul M, SarıtaşYüksel E, İpek S, Vatansever S, et al. An evaluation of the correlation betweenhepcidin serumlevels and disease activity in inflammatory bowel disease. Gastroenterol Res Pract 2015; 2015:1–4.

    Article  Google Scholar 

  24. 24

    Koca SS, Isik A, Ustundag B, Metin K, Aksoy K. Serum pro-hepcidin levels in rheumatoid arthritis and systemic lupus erythematosus. Inflammation 2008; 31:146–153.

    CAS  PubMed  Article  Google Scholar 

  25. 25

    Kim HR, Kim KW, Yoon SJ, Kim SH, Lee SH. Serum pro-hepcidin could reflect disease activity in patients with rheumatoid arthritis. J Korean Med Sci 2010; 25:348–352.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  26. 26

    Adriana S, Valeanu M, Bolosiu HD, Craciun AM. Evaluation of serum hepcidin variations in patients with rheumatoid arthritis according to anemia profile and its correlation with disease activity. Rev Romana Med Lab 2013; 21:17–27.

    Google Scholar 

  27. 27

    Means RT. Recent developments in the anemia of chronic disease. Curr Hematol Rep 2003; 2:116–121.

    PubMed  Article  Google Scholar 

  28. 28

    Roe MA, Spinks C, Heath AL, Harvey LJ, Foxall R, Wimperis J, et al. 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; 97:544–549.

    CAS  PubMed  Article  Google Scholar 

  29. 29

    Nagy J, Lakner L, Poór VS, Pandur E, Mózsik G, Miseta A, et al. Serum prohepcidin levels in chronic inflammatory bowel diseases. J Crohns Colitis 2010; 4:649–653.

    PubMed  Article  Google Scholar 

  30. 30

    Emerah A, Abbas SF, Pasha HF. Serum prohepcidin concentrations in rheumatoid arthritis and its relation to disease activity. Egypt Rheumatol Rehabil 2014; 41:130–134.

    Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Nashwa Ismail Hashaad MD.

Additional information

This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work noncommercially, as long as the author is credited and the new creations are licensed under the identical terms.

Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ganeb, S.S., Hamad, G.A.E., El-Tanawy, R.M. et al. Correlations between Serum prohepcidin level disease activity in rheumatoid arthritis and systemic lupus erythematous. Egypt Rheumatol Rehabil 43, 102–107 (2016).

Download citation


  • prohepcidin
  • rheumatoid arthritis
  • systemic lupus erythematous