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Published in: Current Rheumatology Reports 2/2012

01-04-2012 | PEDIATRIC RHEUMATOLOGY (TJA LEHMAN, SECTION EDITOR)

What Do Cytokine Profiles Tell Us About Subsets of Juvenile Idiopathic Arthritis?

Authors: Rolando Cimaz, Davide Moretti, Ilaria Pagnini, Achille Marino, Luca Cantarini, Gabriele Simonini

Published in: Current Rheumatology Reports | Issue 2/2012

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Abstract

Classification of juvenile idiopathic arthritis is an ongoing process and up to now has been predominantly based on clinical manifestations—mainly number of joints at onset of disease. In the meantime, basic studies have advanced our knowledge regarding the disease pathogenesis. Unfortunately, studies of cytokines and cytokine polymorphisms have not followed the predominantly clinical International League of Associations for Rheumatology classification in that no significant biological differences among the different disease categories have been demonstrated with robust associations. Only systemic-onset disease seems to be quite different from other disease categories with regard to biologic mechanisms; indeed, it now seems closer to autoinflammatory than to classic autoimmune diseases. New players in the immunologic basis of juvenile idiopathic arthritis (eg, interleukin-17 and regulatory T cells) are also discussed in this review.
Literature
1.
go back to reference • Quartier P, Allantaz F, Cimaz R, et al.: A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011, 70:747–54. This was the first placebo-controlled trial of anakinra in SoJIA.PubMedCrossRef • Quartier P, Allantaz F, Cimaz R, et al.: A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis 2011, 70:747–54. This was the first placebo-controlled trial of anakinra in SoJIA.PubMedCrossRef
2.
go back to reference Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005;201:1479–86.PubMedCrossRef Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005;201:1479–86.PubMedCrossRef
3.
go back to reference 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;204:2131–44.PubMedCrossRef 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;204:2131–44.PubMedCrossRef
4.
go back to reference Nigrovic PA, Mannion M, Prince FH, 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;63:545–55.PubMedCrossRef Nigrovic PA, Mannion M, Prince FH, 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;63:545–55.PubMedCrossRef
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference Maeno N, Takei S, Nomura Y, et al. Highly elevated serum levels of interleukin-18 in systemic juvenile idiopathic arthritis but not in other juvenile idiopathic arthritis subtypes or in Kawasaki disease: comment on the article by Kawashima et al. Arthritis Rheum. 2002;46:2539–41.PubMedCrossRef Maeno N, Takei S, Nomura Y, et al. Highly elevated serum levels of interleukin-18 in systemic juvenile idiopathic arthritis but not in other juvenile idiopathic arthritis subtypes or in Kawasaki disease: comment on the article by Kawashima et al. Arthritis Rheum. 2002;46:2539–41.PubMedCrossRef
7.
go back to reference Lotito AP, Campa A, Silva CA, et al. Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis. J Rheumatol. 2007;34:823–30.PubMed Lotito AP, Campa A, Silva CA, et al. Interleukin 18 as a marker of disease activity and severity in patients with juvenile idiopathic arthritis. J Rheumatol. 2007;34:823–30.PubMed
8.
go back to reference Jelusić M, Lukić IK, Tambić-Bukovac L, et al. Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis. Clin Rheumatol. 2007;26:1332–4.PubMedCrossRef Jelusić M, Lukić IK, Tambić-Bukovac L, et al. Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis. Clin Rheumatol. 2007;26:1332–4.PubMedCrossRef
9.
go back to reference Shimizu M, Yokoyama T, Yamada K, et al. Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis. Rheumatology (Oxford). 2010;49:1645–53.CrossRef Shimizu M, Yokoyama T, Yamada K, et al. Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis. Rheumatology (Oxford). 2010;49:1645–53.CrossRef
10.
go back to reference De Jager W, Vastert SJ, Beekman JM, et al. Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2782–93.PubMedCrossRef De Jager W, Vastert SJ, Beekman JM, et al. Defective phosphorylation of interleukin-18 receptor beta causes impaired natural killer cell function in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2782–93.PubMedCrossRef
11.
go back to reference Mörmann M, Rieth H, Hua TD, et al. Mosaics of gene variations in the interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. Genes Immun. 2004;5:246–55.PubMedCrossRef Mörmann M, Rieth H, Hua TD, et al. Mosaics of gene variations in the interleukin-10 gene promoter affect interleukin-10 production depending on the stimulation used. Genes Immun. 2004;5:246–55.PubMedCrossRef
12.
go back to reference Fife MS, Gutierrez A, Ogilvie EM, et al. Novel IL10 gene family associations with systemic juvenile idiopathic arthritis. Arthritis Res Ther. 2006;8:R148.PubMedCrossRef Fife MS, Gutierrez A, Ogilvie EM, et al. Novel IL10 gene family associations with systemic juvenile idiopathic arthritis. Arthritis Res Ther. 2006;8:R148.PubMedCrossRef
13.
go back to reference Möller JC, Paul D, Ganser G, et al. IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA). Clin Exp Rheumatol. 2010;28:912–8.PubMed Möller JC, Paul D, Ganser G, et al. IL10 promoter polymorphisms are associated with systemic onset juvenile idiopathic arthritis (SoJIA). Clin Exp Rheumatol. 2010;28:912–8.PubMed
14.
go back to reference De Kleer IM, Wedderburn LR, Taams LS, et al. CD4 + CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol. 2004;172:6435–43.PubMed De Kleer IM, Wedderburn LR, Taams LS, et al. CD4 + CD25bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol. 2004;172:6435–43.PubMed
15.
go back to reference Nistala K, Wedderburn LR. Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis. Rheumatology (Oxford). 2009;48:602–6.CrossRef Nistala K, Wedderburn LR. Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis. Rheumatology (Oxford). 2009;48:602–6.CrossRef
16.
go back to reference Nistala K, Moncrieffe H, Newton KR, et al. Interleukin-17-producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum. 2008;58:875–87.PubMedCrossRef Nistala K, Moncrieffe H, Newton KR, et al. Interleukin-17-producing T cells are enriched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum. 2008;58:875–87.PubMedCrossRef
17.
go back to reference Olivito B, Simonini G, Ciullini S, et al. Th17 transcription factor RORC2 is inversely correlated with FOXP3 expression in the joints of children with juvenile idiopathic arthritis. J Rheumatol. 2009;36:2017–24.PubMedCrossRef Olivito B, Simonini G, Ciullini S, et al. Th17 transcription factor RORC2 is inversely correlated with FOXP3 expression in the joints of children with juvenile idiopathic arthritis. J Rheumatol. 2009;36:2017–24.PubMedCrossRef
18.
go back to reference • Cosmi L, Cimaz R, Maggi L, et al.: Evidence of the transient nature of the Th17 phenotype of CD4 + CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis. Arthritis Rheum 2011, 63:2504–15. CD161 is a marker of Th17 cells, which are present in the SF but can convert to Th1 under appropriate circumstances.PubMedCrossRef • Cosmi L, Cimaz R, Maggi L, et al.: Evidence of the transient nature of the Th17 phenotype of CD4 + CD161+ T cells in the synovial fluid of patients with juvenile idiopathic arthritis. Arthritis Rheum 2011, 63:2504–15. CD161 is a marker of Th17 cells, which are present in the SF but can convert to Th1 under appropriate circumstances.PubMedCrossRef
19.
go back to reference • Nistala K, Adams S, Cambrook H, et al.: Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci U S A 2010, 107:14751–6. Similar finding as in Cosmi et al. [18•] above, as the clonotypic identity of some Th1 and Th17 cells was also demonstrated.PubMedCrossRef • Nistala K, Adams S, Cambrook H, et al.: Th17 plasticity in human autoimmune arthritis is driven by the inflammatory environment. Proc Natl Acad Sci U S A 2010, 107:14751–6. Similar finding as in Cosmi et al. [18•] above, as the clonotypic identity of some Th1 and Th17 cells was also demonstrated.PubMedCrossRef
20.
go back to reference Van den Ham HJ, de Jager W, Bijlsma JW, et al. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis. Rheumatology (Oxford). 2009;48:899–905.CrossRef Van den Ham HJ, de Jager W, Bijlsma JW, et al. Differential cytokine profiles in juvenile idiopathic arthritis subtypes revealed by cluster analysis. Rheumatology (Oxford). 2009;48:899–905.CrossRef
21.
go back to reference • Barnes MG, Grom AA, Thompson SD, et al. Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:3249–58. This gene expression study shows that not only number of joints, but other parameters (here, age at onset) can be used to classify JIA.PubMedCrossRef • Barnes MG, Grom AA, Thompson SD, et al. Biologic similarities based on age at onset in oligoarticular and polyarticular subtypes of juvenile idiopathic arthritis. Arthritis Rheum. 2010;62:3249–58. This gene expression study shows that not only number of joints, but other parameters (here, age at onset) can be used to classify JIA.PubMedCrossRef
22.
go back to reference Griffin TA, Barnes MG, Ilowite NT, et al. Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets. Arthritis Rheum. 2009;60:2113–23.PubMedCrossRef Griffin TA, Barnes MG, Ilowite NT, et al. Gene expression signatures in polyarticular juvenile idiopathic arthritis demonstrate disease heterogeneity and offer a molecular classification of disease subsets. Arthritis Rheum. 2009;60:2113–23.PubMedCrossRef
23.
go back to reference Barnes MG, Grom AA, Thompson SD, et al. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2102–12.PubMedCrossRef Barnes MG, Grom AA, Thompson SD, et al. Subtype-specific peripheral blood gene expression profiles in recent-onset juvenile idiopathic arthritis. Arthritis Rheum. 2009;60:2102–12.PubMedCrossRef
24.
go back to reference Hunter PJ, Nistala K, Jina N, et al. Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression. Arthritis Rheum. 2010;62:896–907.PubMedCrossRef Hunter PJ, Nistala K, Jina N, et al. Biologic predictors of extension of oligoarticular juvenile idiopathic arthritis as determined from synovial fluid cellular composition and gene expression. Arthritis Rheum. 2010;62:896–907.PubMedCrossRef
25.
go back to reference Macaubas C, Nguyen K, Milojevic D, et al. Oligoarticular and polyarticular JIA: epidemiology and pathogenesis. Nat Rev Rheumatol. 2009;5:616–26.PubMedCrossRef Macaubas C, Nguyen K, Milojevic D, et al. Oligoarticular and polyarticular JIA: epidemiology and pathogenesis. Nat Rev Rheumatol. 2009;5:616–26.PubMedCrossRef
26.
go back to reference Mellins ED, Macaubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol. 2011;7:416–26.PubMedCrossRef Mellins ED, Macaubas C, Grom AA. Pathogenesis of systemic juvenile idiopathic arthritis: some answers, more questions. Nat Rev Rheumatol. 2011;7:416–26.PubMedCrossRef
27.
go back to reference Lin YT, Wang CT, Gershwin ME, Chiang BL. The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis. Autoimmun Rev. 2011;10:482–9.PubMedCrossRef Lin YT, Wang CT, Gershwin ME, Chiang BL. The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis. Autoimmun Rev. 2011;10:482–9.PubMedCrossRef
Metadata
Title
What Do Cytokine Profiles Tell Us About Subsets of Juvenile Idiopathic Arthritis?
Authors
Rolando Cimaz
Davide Moretti
Ilaria Pagnini
Achille Marino
Luca Cantarini
Gabriele Simonini
Publication date
01-04-2012
Publisher
Current Science Inc.
Published in
Current Rheumatology Reports / Issue 2/2012
Print ISSN: 1523-3774
Electronic ISSN: 1534-6307
DOI
https://doi.org/10.1007/s11926-011-0233-3

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