vspВопросы современной педиатрииCurrent Pediatrics1682-55271682-5535Издательство «ПедиатрЪ»10.15690/vsp.v11i3.293vsp-501Research ArticleНЕПРЕРЫВНОЕ ПРОФЕССИОНАЛЬНОЕ ОБРАЗОВАНИЕPROFESSIONAL DEVELOPMENTСИСТЕМНЫЙ ЮВЕНИЛЬНЫЙ ИДИОПАТИЧЕСКИЙ АРТРИТ: МЕХАНИЗМЫ РАЗВИТИЯ, МИШЕНИ ДЛЯ ГЕННО-ИНЖЕНЕРНОЙ БИОЛОГИЧЕСКОЙ ТЕРАПИИSYSTEMIC JUVENILE IDIOPATHIC ARTHRITIS: MECHANISMS OF DEVELOPMENT AND TARGETS FOR GENETIC ENGINEERING BIOLOGICAL THERAPYГромАлексей А.GromAlexei A.

Alexei A. Grom, MD (Алексей А. Гром, доктор медицины), Cincinnati Children’sHospitalMedicalCenter (Педиатрический клинический медицинский центр Цинциннати), Division of Rheumatology, MLC 4010 (Отделение ревматологии, MLC 4010)

alexi.grom@cchmc.orgПедиатрический клинический медицинский центр, отделение ревматологии, Цинциннати, штат ОгайоСоединённые Штаты АмерикиCincinnati Children’s Hospital Medical Center, Division of Rheumatology, MLC 4010, OHUnited States201217052012113Вопросы современной педиатрии2833Copyright © Гром А.А., 20122012Гром А.А.Grom A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vsp.spr-journal.ru/jour/article/view/501

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ReferencesStill G. F. On a form of chronic joint disease in children. Med-Chir. Trans. 1897; 80: 47–59.Still G. F. On a form of chronic joint disease in children. Med-Chir. Trans. 1897; 80: 47–59.Schneider R., Laxer R. M. Systemic onset juvenile rheumatoid arthritis. Baillieres Clin Rheumatol. 1998; 12: 245–271.Schneider R., Laxer R. M. Systemic onset juvenile rheumatoid arthritis. Baillieres Clin Rheumatol. 1998; 12: 245–271.Hadchouel M., Prieur A. M., Griscelli C. Acute hemorrhagic, hepatic, and neurologic manifestations in juvenile rheumatoid arthritis: possible relationship to drugs or infection. J. Pediatr. 1985; 106 (4): 561–566.Hadchouel M., Prieur A. M., Griscelli C. Acute hemorrhagic, hepatic, and neurologic manifestations in juvenile rheumatoid arthritis: possible relationship to drugs or infection. J. Pediatr. 1985; 106 (4): 561–566.Ramanan A. V., Schneider R. Macrophage activation syndrome what's in a name! J. Rheumatol. 2003; 30: 2513–2516.Ramanan A. V., Schneider R. Macrophage activation syndrome what's in a name! J. Rheumatol. 2003; 30: 2513–2516.Athreya B. H. Is macrophage activation syndrome a new entity? Clin. Exp. Rheumatol. 2002; 20: 121–123.Athreya B. H. Is macrophage activation syndrome a new entity? Clin. Exp. Rheumatol. 2002; 20: 121–123.Grom A. A. NK dysfunction: a common pathway in systemic onset juvenile rheumatoid arthritis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Arthritis Rheum. 2004; 50: 689–698.Grom A. A. NK dysfunction: a common pathway in systemic onset juvenile rheumatoid arthritis, macrophage activation syndrome and hemophagocytic lymphohistiocytosis. Arthritis Rheum. 2004; 50: 689–698.Filipovich H. A. Hemophagocytic lymphohistiocytosis. Immunol Allergy Clin. N. Am. 2002; 22: 281–300.Filipovich H. A. Hemophagocytic lymphohistiocytosis. Immunol Allergy Clin. N. Am. 2002; 22: 281–300.Henter J. I., Horne A., Arico M. et al. Diagnostic and therapeutic guidelines for hemopagocytic lymphohistiocytosis. Pediatr. Blood Cancer. 2007; 48: 124–131.Henter J. I., Horne A., Arico M. et al. Diagnostic and therapeutic guidelines for hemopagocytic lymphohistiocytosis. Pediatr. Blood Cancer. 2007; 48: 124–131.Lang B. A. et al. Radiologic features of systemic onset juvenile rheumatoid arthritis. J. Rheumatol. 1995; 22: 168–173.Lang B. A. et al. Radiologic features of systemic onset juvenile rheumatoid arthritis. J. Rheumatol. 1995; 22: 168–173.Lomater C., Gerloni V., Gattinara M. et al. Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J. Rheumatol. 2000; 27: 491–496.Lomater C., Gerloni V., Gattinara M. et al. Systemic onset juvenile idiopathic arthritis: a retrospective study of 80 consecutive patients followed for 10 years. J. Rheumatol. 2000; 27: 491–496.Ramanan A. V., Grom A. A. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology (Oxford). 2005; 44: 1350–1353.Ramanan A. V., Grom A. A. Does systemic-onset juvenile idiopathic arthritis belong under juvenile idiopathic arthritis? Rheumatology (Oxford). 2005; 44: 1350–1353.Frosch M., Roth J. New insights in systemic juvenile idiopathic arthritis — from pathophysiology to treatment. Rheumatology (Oxford). 2008; 47: 121–125.Frosch M., Roth J. New insights in systemic juvenile idiopathic arthritis — from pathophysiology to treatment. Rheumatology (Oxford). 2008; 47: 121–125.Beutler B. Inferences, questions and possibilities in Toll-like receptor signaling. Nature. 2004; 430: 257–263.Beutler B. Inferences, questions and possibilities in Toll-like receptor signaling. Nature. 2004; 430: 257–263.Hull K. M., Shoham N., Chae J. J. et al. The expanding spectrum of systemic autoinflammtory disorders and their rheumatic manifestations. Curr. Opin. Rheumatol. 2003; 15: 61–69.Hull K. M., Shoham N., Chae J. J. et al. The expanding spectrum of systemic autoinflammtory disorders and their rheumatic manifestations. Curr. Opin. Rheumatol. 2003; 15: 61–69.Pascual V., Allantaz F., Arce E. et al. Role of Interleukin-1 in the pathogenesis of systemic juvenile idiopathic arthritis and clinical response to IL-1 blockde. J. Exp. Med. 2005; 201: 1479–1486.Pascual V., Allantaz F., Arce E. et al. Role of Interleukin-1 in the pathogenesis of systemic juvenile idiopathic arthritis and clinical response to IL-1 blockde. J. Exp. Med. 2005; 201: 1479–1486.Fall N., Barnes M., Thornton S. et al. Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum. 2007; 56: 3793–3804.Fall N., Barnes M., Thornton S. et al. Gene expression profiling of peripheral blood from patients with untreated new-onset systemic juvenile idiopathic arthritis reveals molecular heterogeneity that may predict macrophage activation syndrome. Arthritis Rheum. 2007; 56: 3793–3804.Ogilvie E. M., Khan A., Hubank M. et al. Specific gene expression profiles in systemic juvenile idiopathic arthritis. Arthritis Rheum. 2007; 56: 1954–1965.Ogilvie E. M., Khan A., Hubank M. et al. Specific gene expression profiles in systemic juvenile idiopathic arthritis. Arthritis Rheum. 2007; 56: 1954–1965.Barnes M. G., Grom A. A., Thompson S. D. et al. Gene Expression Signatures in new onset untreated juvenile idiopathic arthritis. Arthritis Rheum. 2009; 60: 2101–2112.Barnes M. G., Grom A. A., Thompson S. D. et al. Gene Expression Signatures in new onset untreated juvenile idiopathic arthritis. Arthritis Rheum. 2009; 60: 2101–2112.Allantaz F., Chaussabel D., Stichweh D. et al. Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. J. Exp. Med. 2007; 204: 2131–2144.Allantaz F., Chaussabel D., Stichweh D. et al. Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade. J. Exp. Med. 2007; 204: 2131–2144.Nepom B. G., Glass D. N. Juvenile rheumatoid arthritis and HLA: report of the Park City III workshop. J. Rheumatol. 1992; 33 (Suppl.): 70–74.Nepom B. G., Glass D. N. Juvenile rheumatoid arthritis and HLA: report of the Park City III workshop. J. Rheumatol. 1992; 33 (Suppl.): 70–74.Thompson S. D. et al. A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage. Arthritis Rheum. 2004; 50 (9): 2920–2930.Thompson S. D. et al. A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair families provides evidence of linkage. Arthritis Rheum. 2004; 50 (9): 2920–2930.Fishman D. et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J. Clin. Invest. 1998; 102: 1369–1376.Fishman D. et al. The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J. Clin. Invest. 1998; 102: 1369–1376.Ogilvie E. M. et al. The -174G allele of the interleukin-6 gene confers susceptibility to systemic arthritis in children: a multicenter study using simplex and multiplex juvenile idiopathic arthritis families. Arthritis Rheum. 2003; 48: 3202–3206.Ogilvie E. M. et al. The -174G allele of the interleukin-6 gene confers susceptibility to systemic arthritis in children: a multicenter study using simplex and multiplex juvenile idiopathic arthritis families. Arthritis Rheum. 2003; 48: 3202–3206.Donn R. P. et al. A novel 5'-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemiconset juvenile idiopathic arthritis. Arthritis Rheum. 2001; 44: 1782–1785.Donn R. P. et al. A novel 5'-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemiconset juvenile idiopathic arthritis. Arthritis Rheum. 2001; 44: 1782–1785.De Benedetti F. et al. Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2003; 48: 1398–1407.De Benedetti F. et al. Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2003; 48: 1398–1407.Wittkowski H., Frosch M., Wulffraat N. et al. S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin. Arthritis Rheum. 2008; 58: 3924–3931.Wittkowski H., Frosch M., Wulffraat N. et al. S100A12 is a novel molecular marker differentiating systemic-onset juvenile idiopathic arthritis from other causes of fever of unknown origin. Arthritis Rheum. 2008; 58: 3924–3931.Frosch M., Ahlmann M., Vogl T. et al. The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1beta form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009; 60: 883–891.Frosch M., Ahlmann M., Vogl T. et al. The myeloid-related proteins 8 and 14 complex, a novel ligand of toll-like receptor 4, and interleukin-1beta form a positive feedback mechanism in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009; 60: 883–891.Vogl T., Tenbrock K., Ludwig S. et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat. Med. 2007; 13: 1042–1049.Vogl T., Tenbrock K., Ludwig S. et al. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock. Nat. Med. 2007; 13: 1042–1049.De Benedetti F., Martini A. Is systemic juvenile rheumatoid arthritis an interleukin 6 mediated disease? J. Rheumatol. 1998; 25: 203–207.De Benedetti F., Martini A. Is systemic juvenile rheumatoid arthritis an interleukin 6 mediated disease? J. Rheumatol. 1998; 25: 203–207.De Benedetti F., Massa M., Robbioni P. et al. Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. Arthritis Rheum. 1991; 34: 1158–1163.De Benedetti F., Massa M., Robbioni P. et al. Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. Arthritis Rheum. 1991; 34: 1158–1163.Chai Z., Gatti S., Toniatti C. et al. Interleukin-6 gene expression in the central nervous system is necessary for fever response to lipopolysacharide or IL-1 : a study in IL-6 deficient mice. J. Exp. Med. 1996; 183: 311–316.Chai Z., Gatti S., Toniatti C. et al. Interleukin-6 gene expression in the central nervous system is necessary for fever response to lipopolysacharide or IL-1 : a study in IL-6 deficient mice. J. Exp. Med. 1996; 183: 311–316.Prieur A. M., Roux-Lombard P., Dayer J. M. Dynamics of fever and the cytokine network in systemic juvenile arthritis. Rev. Rhum. Engl. Ed. 1996; 63: 163–170.Prieur A. M., Roux-Lombard P., Dayer J. M. Dynamics of fever and the cytokine network in systemic juvenile arthritis. Rev. Rhum. Engl. Ed. 1996; 63: 163–170.Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 1999; 340: 448.Gabay C., Kushner I. Acute-phase proteins and other systemic responses to inflammation. N. Engl. J. Med. 1999; 340: 448.Rooney M., David J., Symons J. et al. Inflammatory cytokine responses in juvenile chronic arthritis. Br. J. Rheum. 1995; 34: 454.Rooney M., David J., Symons J. et al. Inflammatory cytokine responses in juvenile chronic arthritis. Br. J. Rheum. 1995; 34: 454.Kimura H., Ishibashi T., Uchida T. et al. Interleukin 6 is a differentiation factor for human megakaryocytes in vitro. Eur. J. Immunol. 1990; 20: 1927–1931.Kimura H., Ishibashi T., Uchida T. et al. Interleukin 6 is a differentiation factor for human megakaryocytes in vitro. Eur. J. Immunol. 1990; 20: 1927–1931.D'Hondt V., Humblet Y., Guillaume T. et al. Thrombopoietic effects and toxicity of interleukin-6 in patients with ovarian cancer before and after chemotherapy: a multicentric placebo-controlled, randomized phase Ib study. Blood. 1995; 85: 2347–2353.D'Hondt V., Humblet Y., Guillaume T. et al. Thrombopoietic effects and toxicity of interleukin-6 in patients with ovarian cancer before and after chemotherapy: a multicentric placebo-controlled, randomized phase Ib study. Blood. 1995; 85: 2347–2353.Weiss G., Goodnough L. T. Anemia of chronic disease. N. Engl. J. Med. 2005; 352: 1011–1023.Weiss G., Goodnough L. T. Anemia of chronic disease. N. Engl. J. Med. 2005; 352: 1011–1023.Nemeth E., Rivera S., Gabayan V. et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Invest. 2004; 113: 1271–1276.Nemeth E., Rivera S., Gabayan V. et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J. Clin. Invest. 2004; 113: 1271–1276.Cazzola M., Ponchio L., De B. F. et al. Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. Blood. 1996; 87: 4824–4830.Cazzola M., Ponchio L., De B. F. et al. Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. Blood. 1996; 87: 4824–4830.Hinze C. H., Fall N., Thornton S. et al. Immature cell populations and an erythropoiesis gene expression signature in systemic juvenile idiopathic arthritis: Implications for pathogenesis. Arthritis. Res. Ther. 2010; 12: R123.Hinze C. H., Fall N., Thornton S. et al. Immature cell populations and an erythropoiesis gene expression signature in systemic juvenile idiopathic arthritis: Implications for pathogenesis. Arthritis. Res. Ther. 2010; 12: R123.Guerne P. A., Zuraw B. L., Vaughan J. H. et al. Synovium as a source of interleukin 6 in vitro. Contribution to local and systemic manifestations of arthritis. J. Clin. Invest. 1989; 83: 585–592.Guerne P. A., Zuraw B. L., Vaughan J. H. et al. Synovium as a source of interleukin 6 in vitro. Contribution to local and systemic manifestations of arthritis. J. Clin. Invest. 1989; 83: 585–592.De Benedetti F., Pignatti P., Gerloni et al. Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis. J. Rheumatol. 1997; 24: 1403–1409.De Benedetti F., Pignatti P., Gerloni et al. Differences in synovial fluid cytokine levels between juvenile and adult rheumatoid arthritis. J. Rheumatol. 1997; 24: 1403–1409.Eberhardt B. A., Laxer R. M., Andersson U. et al. Local synthesis of both macrophage and T cell cytokines by synovial cells from children with Juvenile rheumatoid arthritis. Clin. Exp. Immunol. 1994; 96: 260–266.Eberhardt B. A., Laxer R. M., Andersson U. et al. Local synthesis of both macrophage and T cell cytokines by synovial cells from children with Juvenile rheumatoid arthritis. Clin. Exp. Immunol. 1994; 96: 260–266.Romano M., Sironi M., Toniatti C. et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997; 6: 315–325.Romano M., Sironi M., Toniatti C. et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity. 1997; 6: 315–325.Alonzi T., Fattori E., Lazzaro D. et al. Interleukin 6 is required for the development of collagen-induced arthritis. J. Exp Med. 1998; 187 (4): 461–468.Alonzi T., Fattori E., Lazzaro D. et al. Interleukin 6 is required for the development of collagen-induced arthritis. J. Exp Med. 1998; 187 (4): 461–468.Tamura T., Udagawa N., Takahashi N. et al. Soluble interleukin- 6 receptor triggers osteoclast formation by interleukin 6. Proc. Natl. Acad. Sci. USA. 1993; 90: 11924–11928.Tamura T., Udagawa N., Takahashi N. et al. Soluble interleukin- 6 receptor triggers osteoclast formation by interleukin 6. Proc. Natl. Acad. Sci. USA. 1993; 90: 11924–11928.Legendre F., Dudhia J., Pujol J. P., Bogdanowicz P. J. AK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a downregulation of SOX9 expression. J. Biol. Chem. 2003; 278: 2903.Legendre F., Dudhia J., Pujol J. P., Bogdanowicz P. J. AK/STAT but not ERK1/ERK2 pathway mediates interleukin (IL)-6/soluble IL-6R down-regulation of Type II collagen, aggrecan core, and link protein transcription in articular chondrocytes. Association with a downregulation of SOX9 expression. J. Biol. Chem. 2003; 278: 2903.Ansell B. M., Bywaters E. G. Growth in Still’s disease. Ann. Rheum. Dis. 1956; 15: 295–319.Ansell B. M., Bywaters E. G. Growth in Still’s disease. Ann. Rheum. Dis. 1956; 15: 295–319.De Benedetti F., Alonzi T., Moretta A. et al. Interleukin-6 causes growth impairment in transgenic mice through a decrease in Insulinlike growth factor 1: a model of stunted growth in children with chronic inflammation. J. Clin. Invest. 1997; 99: 643–650.De Benedetti F., Alonzi T., Moretta A. et al. Interleukin-6 causes growth impairment in transgenic mice through a decrease in Insulinlike growth factor 1: a model of stunted growth in children with chronic inflammation. J. Clin. Invest. 1997; 99: 643–650.De Benedetti F., Rucci N., Del Fattore A. et al. Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis&Rheum. 2006; 54: 3551.De Benedetti F., Rucci N., Del Fattore A. et al. Impaired skeletal development in interleukin-6-transgenic mice: a model for the impact of chronic inflammation on the growing skeletal system. Arthritis&Rheum. 2006; 54: 3551.Yokota S., Imagawa T., Mori M. et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008; 371: 998–1006.Yokota S., Imagawa T., Mori M. et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet. 2008; 371: 998–1006.Yutaka I., Ozawa R., Imagawa T. et al. Radiographic improvement of damaged large joints in children with systemic juvenile idiopathic arthritis following tocilizumab. Ann. Rheum Dis. 2011; Epub ahead of print.Yutaka I., Ozawa R., Imagawa T. et al. Radiographic improvement of damaged large joints in children with systemic juvenile idiopathic arthritis following tocilizumab. Ann. Rheum Dis. 2011; Epub ahead of print.Verbsky J. W., White A. J. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J. Rheumatol. 2004; 31: 2071–2075.Verbsky J. W., White A. J. Effective use of the recombinant interleukin 1 receptor antagonist anakinra in therapy resistant systemic onset juvenile rheumatoid arthritis. J. Rheumatol. 2004; 31: 2071–2075.Irigoyen P. I., Olson J., Hom C., Ilowite N. T. Treatment of systemic onset juvenile rheumatoid arthritis with anakinra. Arthritis Rheum. 2004; 50 (Suppl): S437.Irigoyen P. I., Olson J., Hom C., Ilowite N. T. Treatment of systemic onset juvenile rheumatoid arthritis with anakinra. Arthritis Rheum. 2004; 50 (Suppl): S437.Henrickson M. Efficacy of anakinra in refractory systemic arthritis. Arthritis Rheum. 2004; 50 (Suppl): S438.Henrickson M. Efficacy of anakinra in refractory systemic arthritis. Arthritis Rheum. 2004; 50 (Suppl): S438.Prieur A. M. et al. Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis. Lancet. 1987; 2 (8570): 1240–1242.Prieur A. M. et al. Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis. Lancet. 1987; 2 (8570): 1240–1242.Gattorno M., Piccini A., Lasiglie D. et al. The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2008; 58: 1505–1515.Gattorno M., Piccini A., Lasiglie D. et al. The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2008; 58: 1505–1515.Quartier P., Allantaz F., Cimaz R. et al. A multicenter, randomized, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS). Ann Rheum Dis. 2011; 70: 747–754.Quartier P., Allantaz F., Cimaz R. et al. A multicenter, randomized, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS). Ann Rheum Dis. 2011; 70: 747–754.Nigrovic P., Mannion M., Prince F. H. et al. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 2011; 63: 545–555.Nigrovic P., Mannion M., Prince F. H. et al. Anakinra as first-line disease-modifying therapy in systemic juvenile idiopathic arthritis: report of forty-six patients from an international multicenter series. Arthritis Rheum. 2011; 63: 545–555.

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