ymjЯкутский медицинский журналYakut Medical Journal1813-19052312-1017ЯНЦ КМПymj-1769Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHРоль гепсидина в развитии анемии у пациентов с ювенильным ревматоидным артритомThe role of hepcidin in the development of anemia in patients with juvenile rheumatoid arthritisЕгоровА. С.EgorovA. S.

Егоров Андрей Сергеевич – ст. лаб.

Egorov Andrey S. – senior assistant

ФедороваЕ. В.FedorovaE. V.

Федорова Елена Владимировна – аспирант

Fedorova Elena V., assistant

ЧасныкВ. Г.ChasnykV. G.

Часнык Вячеслав Григорьевич – д.м.н., проф.

MD, professor

chasnyk@gmail.comВинокуроваФ. В.VinokurovaF. V.

Винокурова Фекла Васильевна – м.н.с.

junior researcher

Yakutsk

Санкт-Петербургский гос. педиатрич. мед. университетРоссияSPbSPMARussian FederationЯНЦ КМП СО РАМНРоссияYSC CMP SB RAMSRussian Federation201330092025024245Copyright © Егоров А.С., Федорова Е.В., Часнык В.Г., Винокурова Ф.В., 20252025Егоров А.С., Федорова Е.В., Часнык В.Г., Винокурова Ф.В.Egorov A.S., Fedorova E.V., Chasnyk V.G., Vinokurova F.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://ymj.elpub.ru/jour/article/view/1769

Считается, что гиперпродукция гепсидина в печени, обусловленная влиянием высокого уровня провоспалительных цитокинов, в первую очередь интерлейкина-6, играет ведущую роль в развитии анемии у пациентов с ювенильным ревматоидным артритом. По результатам обследования пациентов с ювенильным ревматоидным артритом, получающих терапию биологическими болезнь-модифицирующими лекарственными средствами (тоцилизумаб и голимумаб), прямой связи между уровнем гемоглобина и гепсидина не выявлено. Наиболее вероятно, что анемия при ревматоидном артрите обусловлена множеством факторов и связана как с нарушением метаболизма железа в организме, так и с негативным влиянием провоспалительных цитокинов на эритропоэз. Развитие тяжелой анемии, вероятно, сопряжено с сопутствующим дефицитом железа либо с развитием синдрома макрофагальной активации у детей с ювенильным ревматоидным артритом.

Overproduction of hepcidin in the liver is considered to be due to the effect of high levels of proinflammatory cytokines. Interleukin-6 is known to play a key role in the development of anemia in patients with juvenile rheumatoid arthritis. During the study of patients with juvenile rheumatoid arthritis treated with biological disease-modifying drugs (tocilizumab and golimumab), direct relations between the level of hemoglobin and hepcidin were not found. Most probable, anemia in rheumatoid arthritis is multifactorial and involves violation of iron metabolism in the organism and the negative effects of proinflammatory cytokines on erythropoiesis. Severe anemia can be associated with iron deficiency or with the macrophage activation syndrome in children with juvenile rheumatoid arthritis.

гепсидинанемияювенильный ревматоидный артритhepcidinanemiajuvenile rheumatoid arthritisReferencesЕгоров А.С. Распространенность анемии у пациентов с ювенильным ревматоидным артритом / А.С. Егоров, Е.В. Федорова // Ревматология в реальной клинической практике: VII всероссийская конференция. – Владимир, 2012. – С.21.Egorov A.S. The prevalence of anemia in patients with juvenile rheumatoid arthritis/ A.S. Egorov, E.V. Fedorova // Rheumatology in clinical practice: VII National Conference. – Vladimir, 2012. – Р.21.Association between serum inflammatory cytokines and disease activity in juvenile idiopathic arthritis/ L.S. Ou, L.C. See, C.J. Wu [et al.] //Clin Rheumatol. 2002 Feb;21(1):52-6.Association between serum inflammatory cytokines and disease activity in juvenile idiopathic arthritis/ L.S. Ou, L.C. See, C.J. Wu [et al.] //Clin Rheumatol. 2002 Feb;21(1):52-6.Association of anemia and physical disability among patients with rheumatoid arthritis/ C. Han, M.U. Rahman, M.K. Doyle [et al.] // J Rheumatol. 2007 Nov;34(11):2177-82.Association of anemia and physical disability among patients with rheumatoid arthritis/ C. Han, M.U. Rahman, M.K. Doyle [et al.] // J Rheumatol. 2007 Nov;34(11):2177-82.Bijlsma J.W. Methotrexate: still the anchor drug in RA treatment / J.W. Bijlsma, J.W. Jacobs // Joint Bone Spine. 2009 Oct;76(5):452-4.Bijlsma J.W. Methotrexate: still the anchor drug in RA treatment / J.W. Bijlsma, J.W. Jacobs // Joint Bone Spine. 2009 Oct;76(5):452-4.Cartwright G.E. The anemia of infection. A review / G.E. Cartwright, M.M. Wintrobe // Adv Intern Med. 1952;5:165–226.Cartwright G.E. The anemia of infection. A review / G.E. Cartwright, M.M. Wintrobe // Adv Intern Med. 1952;5:165–226.CHARISMA Study Group. Doubleblind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate/ R.N. Maini, P.C. Taylor, J. Szechinski [et al.] // Arthritis Rheum. 2006 Sep;54(9):2817-29.CHARISMA Study Group. Doubleblind randomized controlled clinical trial of the interleukin-6 receptor antagonist, tocilizumab, in European patients with rheumatoid arthritis who had an incomplete response to methotrexate/ R.N. Maini, P.C. Taylor, J. Szechinski [et al.] // Arthritis Rheum. 2006 Sep;54(9):2817-29.Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation / T. Ganz // Blood. 2003 Aug 1;102(3):783-8.Ganz T. Hepcidin, a key regulator of iron metabolism and mediator of anemia of inflammation / T. Ganz // Blood. 2003 Aug 1;102(3):783-8.Hepcidin, a urinary antimicrobial peptide synthesized in the liver/ C.H. Park, E.V. Valore, A.J. Waring [et al.] // The Journal of Biological Chemistry. 2001. Vol. 276, No. 11: 7806–7810.Hepcidin, a urinary antimicrobial peptide synthesized in the liver/ C.H. Park, E.V. Valore, A.J. Waring [et al.] // The Journal of Biological Chemistry. 2001. Vol. 276, No. 11: 7806–7810.Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood / G. Peslova, J. Petrak, K. Kuzelova [et al.] //Blood. 2009 Jun 11; 113(24):6225-36.Hepcidin, the hormone of iron metabolism, is bound specifically to alpha-2-macroglobulin in blood / G. Peslova, J. Petrak, K. Kuzelova [et al.] //Blood. 2009 Jun 11; 113(24):6225-36.IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin/ E. Nemeth, S. Rivera, V. Gabayan [et al.] // J Clin Invest. 2004 May; 113(9): 1271-6.IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin/ E. Nemeth, S. Rivera, V. Gabayan [et al.] // J Clin Invest. 2004 May; 113(9): 1271-6.Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to diseasemodifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study / M.C. Genovese, J.D. McKay, E.L. Nasonov [et al.] // Arthritis Rheum. 2008 Oct; 58(10):2968-80.Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to diseasemodifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study / M.C. Genovese, J.D. McKay, E.L. Nasonov [et al.] // Arthritis Rheum. 2008 Oct; 58(10):2968-80.Jayaranee S. Serum prohepcidin concentrations in rheumatoid arthritis/ S. Jayaranee, P. Sthaneshwar, S. Sokkalingam // Pathology. 2009 Feb; 41(2):178-82.Jayaranee S. Serum prohepcidin concentrations in rheumatoid arthritis/ S. Jayaranee, P. Sthaneshwar, S. Sokkalingam // Pathology. 2009 Feb; 41(2):178-82.LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity / A. Krause, S. Neitz, H.J. Mägert [et al.] // FEBS Lett. 2000 Sep 1; 480(2-3):147-50.LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity / A. Krause, S. Neitz, H.J. Mägert [et al.] // FEBS Lett. 2000 Sep 1; 480(2-3):147-50.Masson C.J. Rheumatoid anemia Rev / C.J. Masson // Joint Bone Spine 78 (2011) 131–137.Masson C.J. Rheumatoid anemia Rev / C.J. Masson // Joint Bone Spine 78 (2011) 131–137.Means R.T. Jr. Hepcidin and anaemia/ R.T. Jr. Means // Blood Rev. 2004 Dec; 18(4):219-25.Means R.T. Jr. Hepcidin and anaemia/ R.T. Jr. Means // Blood Rev. 2004 Dec; 18(4):219-25.Means R.T. Jr. Recent developments in the anemia of chronic disease/ R.T.Jr. Means / /Curr Hematol Rep. 2003; 2(2):116.Means R.T. Jr. Recent developments in the anemia of chronic disease/ R.T.Jr. Means / /Curr Hematol Rep. 2003; 2(2):116.Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature/ A. Wilson, H.T. Yu, L.T. Goodnough [et al.] // Am J Med. 2004 Apr 5; 116 Suppl 7A:50S57S.Prevalence and outcomes of anemia in rheumatoid arthritis: a systematic review of the literature/ A. Wilson, H.T. Yu, L.T. Goodnough [et al.] // Am J Med. 2004 Apr 5; 116 Suppl 7A:50S57S.Prevalence of low hemoglobin levels and associations with other disease parameters in rheumatoid arthritis patients: evidence from the CORRONA registry/ D.E. Furst, H. Chang, J.D. Greenberg [et al.] // Clin Exp Rheumatol. 2009 Jul-Aug; 27(4):560-6.Prevalence of low hemoglobin levels and associations with other disease parameters in rheumatoid arthritis patients: evidence from the CORRONA registry/ D.E. Furst, H. Chang, J.D. Greenberg [et al.] // Clin Exp Rheumatol. 2009 Jul-Aug; 27(4):560-6.Serum pro-hepcidin levels in rheumatoid arthritis and systemic lupus erythematosus/ S.S. Koca., A. Isik, B. Ustundag [et al.] // Inflammation. 2008 Jun;31(3):146-53.Serum pro-hepcidin levels in rheumatoid arthritis and systemic lupus erythematosus/ S.S. Koca., A. Isik, B. Ustundag [et al.] // Inflammation. 2008 Jun;31(3):146-53.Synthetic hepcidin causes rapid dosedependent hypoferremia and is concentrated in ferroportin-containing organs / S. Rivera, E. Nemeth, V. Gabayan [et al.] // Blood. 2005 September 15; 106(6): 2196–2199.Synthetic hepcidin causes rapid dosedependent hypoferremia and is concentrated in ferroportin-containing organs / S. Rivera, E. Nemeth, V. Gabayan [et al.] // Blood. 2005 September 15; 106(6): 2196–2199.The iron exporter ferroportin / Slc40a1 is essential for iron homeostasis / A. Donovan, C.A. Lima, J.L. Pinkus [et al.] // Cell Metab. 2005 Mar; 1(3):191-200.The iron exporter ferroportin / Slc40a1 is essential for iron homeostasis / A. Donovan, C.A. Lima, J.L. Pinkus [et al.] // Cell Metab. 2005 Mar; 1(3):191-200.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 / M.K. Doyle, M.U. Rahman, C. Han et [et al.] // Semin Arthritis Rheum. 2009 Oct; 39(2):123-31.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 / M.K. Doyle, M.U. Rahman, C. Han et [et al.] // Semin Arthritis Rheum. 2009 Oct; 39(2):123-31.Young A. Extra-articular manifestations and complications of rheumatoid arthritis / A. Young, G. Koduri // Best Pract Res Clin Rheumatol. 2007 Oct; 21(5):907-27.Young A. Extra-articular manifestations and complications of rheumatoid arthritis / A. Young, G. Koduri // Best Pract Res Clin Rheumatol. 2007 Oct; 21(5):907-27.

The authors declare that there are no conflicts of interest present.