Hepcidin: a promising marker for differential diagnosis of anemia and macrophage activation syndrome in children with juvenile idiopathic arthritis


Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription or Fee Access

Abstract

Hepcidin is a 25-amino acid peptide, which is a key systemic regulator of iron metabolism. As considered, overproduction of hepcidin in the liver is controlled by high levels of proinflammatory cytokines. Is it known that interleukin-6 play a key role in the development of anemia in patients with juvenile idiopathic arthritis (JIA). However, IL-6 blockers itself may provoke the onset of Macrophage Activation Syndrome (MAS), manifesting, particularly, also with anemia. In view of the fact that macrophages involved in MAS express CD163 - a scavenger receptor that binds hemoglobin-haptoglobin complexes - and activate the pathways which are important for adaptation to oxidative stress induced by free iron, we can consider hepcidin as a welcome challenge to predict the development of MAS early in the course of the disease. During the study of 35 patients with JIA treated with biological disease-modifying drugs (tocilizumab and golimumab), direct relations between the level of hemoglobin and hepcidin were not found. However, it was found that the mean corpuscular hemoglobin level is associated with hepcidin concentration in patients with JIA. It was found that concentration of serum hepcidin may be used for early differential diagnosis of anemia and MAS in patients with JIA. High probability of evolution of anemia to MAS was found when concentration of hepcidin was <140 ng/mL and ferritin >160 g/L. The following combinations were associated with high probability of evolution of slight anemia to a severe form, but not to MAS: 1. hepcidin >200 ng/mL and ferritin <140 g/L; 2. hepcidin >140 ng/mL and soluble transferrin receptor <1.6 mg/L; 3. hepcidin >140 ng/mL and total iron binding capacity >46 mcmol/L. Misclassification should be assessed during further studies.

Full Text

Restricted Access

About the authors

Andrey Sergeyevich Egorov

Saint Petersburg State Pediatric Medical University

Email: egorov.doc@gmail.com
MD, Research Fellow, Chair of Hospital Pediatrics

Elena Vladimirovna Fedorova

Saint Petersburg State Pediatric Medical University

Email: detymedic@mail.ru
MD, Research Fellow, Chair of Hospital Pediatrics

Vyacheslav Grigoryevich Chasnyk

Saint Petersburg State Pediatric Medical University

Email: chasnyk@gmail.com
MD, PhD, Dr Med Sci, Professor, Head of the Department of Hospital Pediatrics

Mikhail Mikhaylovich Kostik

Saint Petersburg State Pediatric Medical University

Email: mikhail.kostik@gmail.com
MD, PhD, Associate Professor, Chair of Hospital Pediatrics

Ludmila Stepanovna Snegireva

Saint Petersburg State Pediatric Medical University

Email: l.s.snegireva@mail.ru
MD, Department of Pediatrics N 3

Olga Valeryevna Kalashnikova

Saint Petersburg State Pediatric Medical University

Email: koira7@yandex.ru
MD, PhD, Associate Professor, Chair of Hospital Pediatrics

Margarita Fedorovna Dubko

Saint Petersburg State Pediatric Medical University

Email: andrq@rambler.ru
MD, PhD, Associate Professor, Chair of Hospital Pediatrics

Vera Vasilyevna Masalova

Saint Petersburg State Pediatric Medical University

Email: masalova.vera@gmail.com
MD, Research Fellow, Chair of Hospital Pediatrics

Tatyana Serafimovna Likhacheva

Saint Petersburg State Pediatric Medical University

Email: tatianasl@list.ru
MD, Research Fellow, Chair of Hospital Pediatrics

References

  1. Yegorov A.S., Fedorova E. V. Rasprostranennost anemii u patsiyentov s yuvenilnym revmatoidnym artritom [The prevalence of anemia in patients with juvenile rheumatoid arthritis]. VII Vserossiyskaya konferentsiya “Revmatologiya v realnoy klinicheskoy praktike”: sbornik materialov konferentsii. Vladimir. 2012: 21.
  2. Bijlsma J. W., Jacobs J. W. Methotrexate: still the anchor drug in RA treatment. Joint Bone Spine. 2009; 76 (5): 452-4.
  3. Cartwright G. E., Wintrobe M. M. The anemia of infection. A review. Adv Intern Med. 1952; 5: 165-226.
  4. Donovan A., Lima C. A., Pinkus J. L., Pinkus G. S., Zon L. I., Robine S., Andrews N. C. The iron exporter ferroportin/Slc40a1 is essential for iron homeostasis. Cell Metab. 2005; 1 (3): 191-200.
  5. Doyle M. K., Rahman M. U., Han C., Han J., Giles J., Bingham C. O., Bathon J. Treatment with infliximab plus methotrexate improves anemia in patients with rheumatoid arthritis independent of improvement in other clinical outcome measures-a pooled analysis from three large, multicenter, double-blind, randomized clinical trials. Semin Arthritis Rheum. 2009; 39 (2): 123-31.
  6. Furst D. E., Chang H., Greenberg J. D., Ranganath V. K., Reed G., Ozturk Z. E., Kremer J. M. Prevalence of low hemoglobin levels and associations with other disease parameters in rheumatoid arthritis patients: evidence from the CORRONA registry. Clin Exp Rheumatol. 2009; 27 (4): 560-6.
  7. Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation. Blood. 2003; 102 (3): 783-8.
  8. Genovese M. C., McKay J. D., Nasonov E. L., Mysler E. F., da Silva N. A., Alecock E., Woodworth T., Gomez-Reino J. J. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum. 2008; 58 (10): 2968-80.
  9. Han C., Rahman M. U., Doyle M. K., Bathon J. M., Smolen J., Kavanaugh A., Westhovens R., St Clair E. W., Baker D., Bala M. Association of anemia and physical disability among patients with rheumatoid arthritis. J Rheumatol. 2007; 34 (11): 2177-82.
  10. Jayaranee S., Sthaneshwar P., Sokkalingam S. Serum prohepcidin concentrations in rheumatoid arthritis. Pathology. 2009;41 (2):178-82.
  11. Koca S. S., Isik A., Ustundag B., Metin K., Aksoy K. Serum pro-hepcidin levels in rheumatoid arthritis and systemic lupus erythematosus. Inflammation. 2008; 31 (3): 146-53.
  12. Krause A., Neitz S., Mägert H. J., Schulz A., Forssmann W. G., Schulz-Knappe P., Adermann K. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 2000; 480 (2-3): 147-50.
  13. Maini R. N., Taylor P. C., Szechinski J., Pavelka K., Bröll J., Balint G., Emery P., Raemen F., Petersen J., Smolen J., Thomson D., Kishimoto T. CHARISMA Study Group. Double-blind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate. Arthritis Rheum. 2006; 54 (9): 2817-29.
  14. Masson C. J. Rheumatoid anemia Rev. Joint Bone Spine. 2011; 78: 131-37.
  15. Means R. T. Jr. Hepcidin and anaemia. Blood Rev. 2004; 18 (4): 219-25.
  16. Means R. T. Jr. Recent developments in the anemia of chronic disease. Curr Hematol Rep. 2003; 2 (2): 116.
  17. Nemeth E., Rivera S., Gabayan V., Keller C., Taudorf S., Pedersen B. K., Ganz T. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004; 113 (9): 1271-6.
  18. Ou L. S., See L. C., Wu C. J., Kao C. C., Lin Y. L., Huang J. L. Association between serum inflammatory cytokines and disease activity in juvenile idiopathic arthritis. Clin Rheumatol. 2002; 21 (1): 52-6.
  19. Park C. H., Valore E. V., Waring A. J., Ganz T. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. The Journal of Biological Chemistry. 2001; 276 (11): 7806-10.
  20. Peslova G., Petrak J., Kuzelova K., Hrdy I., Halada P., Kuchel P. W., Soe-Lin S., Ponka P., Sutak R., Becker E., Huang M. L., Suryo Rahmanto Y., Richardson D. R., Vyoral D. Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood. Blood. 2009; 113 (24): 6225-36.
  21. Rivera S., Nemeth E., Gabayan V., Lopez M. A., Farshidi D., Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood. 2005; 106 (6): 2196-9.
  22. Wilson A., Yu H. T., Goodnough L. T., Nissenson A. R. Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature. Am J Med. 2004; 116 (7A): 50-7.
  23. Young A., Koduri G. Extra-articular manifestations and complications of rheumatoid arthritis. Best Pract Res Clin Rheumatol. 2007; 21 (5): 907-27.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2014 Egorov A.S., Fedorova E.V., Chasnyk V.G., Kostik M.M., Snegireva L.S., Kalashnikova O.V., Dubko M.F., Masalova V.V., Likhacheva T.S.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 69634 от 15.03.2021 г.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies