J Rheum Dis.  2020 Oct;27(4):233-240. 10.4078/jrd.2020.27.4.233.

Role of Biomarkers in Juvenile Idiopathic Arthritis

Affiliations
  • 1Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, Korea

Abstract

The aim of this review was to identify the utility of biomarkers used in the diagnosis and the monitoring and treatment of Juvenile idiopathic arthritis (JIA). JIA is a heterogeneous group of diseases characterized by arthritis of unknown etiology that lasts for at least 6 weeks, with onset before the age of 16 years. Unlike adult rheumatoid arthritis, JIA is a heterogeneous arthritis with different subtypes. The diagnosis of JIA is based on clinical evaluation and often involves ruling out other causes of arthritis. Many biomarkers have been studied or are under development to define the classifications of JIA, assess disease activity, predict disease course, treatment response, or the risk of relapse. The diagnostic and prognostic use of biomarkers in JIA could be applied differently depending on diverse subtypes or individuals. To obtain the best clinical outcomes in JIA, it is important to understand the pathophysiology of each JIA subtype and to select and use appropriate biomarkers.

Keyword

Juvenile idiopathic arthritis; Biomarkers; Outcome measures

Reference

1. Harris JG, Kessler EA, Verbsky JW. 2013; Update on the treatment of juvenile idiopathic arthritis. Curr Allergy Asthma Rep. 13:337–46. DOI: 10.1007/s11882-013-0351-2. PMID: 23605168. PMCID: PMC3729726.
Article
2. Prakken B, Albani S, Martini A. 2011; Juvenile idiopathic arthritis. Lancet. 377:2138–49. DOI: 10.1016/S0140-6736(11)60244-4. PMID: 33036309. PMCID: PMC7134528.
Article
3. Kim KH, Kim DS. 2010; Juvenile idiopathic arthritis: diagnosis and differential diagnosis. Korean J Pediatr. 53:931–5. DOI: 10.3345/kjp.2010.53.11.931. PMID: 21218014. PMCID: PMC3012272.
Article
4. Aggarwal R, Ringold S, Khanna D, Neogi T, Johnson SR, Miller A, et al. 2015; Distinctions between diagnostic and classification criteria? Arthritis Care Res (Hoboken). 67:891–7. DOI: 10.1002/acr.22583. PMID: 25776731. PMCID: PMC4482786.
Article
5. Petty RE, Southwood TR, Manners P, Baum J, Glass DN, Goldenberg J, et al. International League of Associations for Rheumatology. 2004; International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol. 31:390–2. PMID: 14760812.
6. Fink CW. 1995; Proposal for the development of classification criteria for idiopathic arthritides of childhood. J Rheumatol. 22:1566–9. PMID: 7473484.
7. Petty RE, Southwood TR, Baum J, Bhettay E, Glass DN, Manners P, et al. 1998; Revision of the proposed classification criteria for juvenile idiopathic arthritis: Durban, 1997. J Rheumatol. 25:1991–4. PMID: 10852298.
8. Martini A. 2012; It is time to rethink juvenile idiopathic arthritis classification and nomenclature. Ann Rheum Dis. 71:1437–9. DOI: 10.1136/annrheumdis-2012-201388. PMID: 22679300.
Article
9. Martini A. 2003; Are the number of joints involved or the presence of psoriasis still useful tools to identify homogeneous disease entities in juvenile idiopathic arthritis? J Rheumatol. 30:1900–3.
10. Martini A, Ravelli A, Avcin T, Beresford MW, Burgos-Vargas R, Cuttica R, et al. Pediatric Rheumatology International Trials Organization (PRINTO). 2019; Toward new classification criteria for juvenile idiopathic arthritis: first steps, Pediatric Rheumatology International Trials Organization international consensus. J Rheumatol. 46:190–7. DOI: 10.3899/jrheum.180168. PMID: 30275259.
Article
11. Ingegnoli F, Castelli R, Gualtierotti R. 2013; Rheumatoid factors: clinical applications. Dis Markers. 35:727–34. DOI: 10.1155/2013/726598. PMID: 24324289.
Article
12. Petty RE, Laxer RM, Wedderburn LR. Petty RE, Laxer RM, Lindsley CB, Wedderburn LR, editors. 2016. Juvenile idiopathic arthritis. Textbook of pediatric rheumatology. 7th ed. Elsevier;Philadelphia: p. 188–204.e6. DOI: 10.1016/B978-0-323-24145-8.00015-6.
Article
13. Bowness P. 2002; HLA B27 in health and disease: a double-edged sword? Rheumatology (Oxford). 41:857–68. DOI: 10.1093/rheumatology/41.8.857. PMID: 12154202.
Article
14. Akikusa J, Choo S. Petty RE, Laxer RM, Lindsley CB, Wedderburn LR, editors. 2016. Laboratory investigations. Textbook of pediatric rheumatology. 7th ed. Elsevier;Philadelphia: p. 117–28.e6. DOI: 10.1016/B978-0-323-24145-8.00010-7.
Article
15. Saurenmann RK, Levin AV, Feldman BM, Laxer RM, Schneider R, Silverman ED. 2010; Risk factors for development of uveitis differ between girls and boys with juvenile idiopathic arthritis. Arthritis Rheum. 62:1824–8. DOI: 10.1002/art.27416. PMID: 20178126.
Article
16. Angeles-Han ST, Pelajo CF, Vogler LB, Rouster-Stevens K, Kennedy C, Ponder L, et al. CARRA Registry Investigators. 2013; Risk markers of juvenile idiopathic arthritis-associated uveitis in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry. J Rheumatol. 40:2088–96. DOI: 10.3899/jrheum.130302. PMID: 24187099. PMCID: PMC4117408.
Article
17. Tebo AE, Jaskowski T, Davis KW, Whiting A, Clifford B, Zeft A, et al. 2012; Profiling anti-cyclic citrullinated peptide antibodies in patients with juvenile idiopathic arthritis. Pediatr Rheumatol Online J. 10:29. DOI: 10.1186/1546-0096-10-29. PMID: 22931121. PMCID: PMC3490766.
Article
18. Swart JF, de Roock S, Prakken BJ. 2016; Understanding inflammation in juvenile idiopathic arthritis: how immune biomarkers guide clinical strategies in the systemic onset subtype. Eur J Immunol. 46:2068–77. DOI: 10.1002/eji.201546092. PMID: 27461267.
Article
19. Pepys MB, Hirschfield GM. 2003; C-reactive protein: a critical update. J Clin Invest. 111:1805–12. DOI: 10.1172/JCI200318921. PMID: 12813013. PMCID: PMC161431.
Article
20. Consolaro A, Ruperto N, Bazso A, Pistorio A, Magni-Manzoni S, Filocamo G, et al. Paediatric Rheumatology International Trials Organisation. 2009; Development and validation of a composite disease activity score for juvenile idiopathic arthritis. Arthritis Rheum. 61:658–66. DOI: 10.1002/art.24516. PMID: 19405003.
Article
21. Cassidy JT, Levinson JE, Bass JC, Baum J, Brewer EJ Jr, Fink CW, et al. 1986; A study of classification criteria for a diagnosis of juvenile rheumatoid arthritis. Arthritis Rheum. 29:274–81. DOI: 10.1002/art.1780290216. PMID: 3485433.
Article
22. Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, et al. 2013; Functions of S100 proteins. Curr Mol Med. 13:24–57. DOI: 10.2174/156652413804486214. PMID: 22834835. PMCID: PMC3707951.
Article
23. Austermann J, Spiekermann C, Roth J. 2018; S100 proteins in rheumatic diseases. Nat Rev Rheumatol. 14:528–41. DOI: 10.1038/s41584-018-0058-9. PMID: 30076385.
Article
24. Foell D, Roth J. 2004; Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum. 50:3762–71. DOI: 10.1002/art.20631. PMID: 15593206.
Article
25. Holzinger D, Frosch M, Kastrup A, Prince FH, Otten MH, Van Suijlekom-Smit LW, et al. 2012; The Toll-like receptor 4 agonist MRP8/14 protein complex is a sensitive indicator for disease activity and predicts relapses in systemic-onset juvenile idiopathic arthritis. Ann Rheum Dis. 71:974–80. DOI: 10.1136/annrheumdis-2011-200598. PMID: 22267331.
Article
26. de Jager W, Hoppenreijs EP, Wulffraat NM, Wedderburn LR, Kuis W, Prakken BJ. 2007; Blood and synovial fluid cytokine signatures in patients with juvenile idiopathic arthritis: a cross-sectional study. Ann Rheum Dis. 66:589–98. DOI: 10.1136/ard.2006.061853. PMID: 17170049. PMCID: PMC1954617.
Article
27. Emonard H, Grimaud JA. 1990; Matrix metalloproteinases. A review. Cell Mol Biol. 36:131–53. DOI: 10.1016/bs.pmbts.2017.02.005. PMID: 28413025. PMCID: PMC5430303.
28. Myles A, Aggarwal A. 2011; Expression of Toll-like receptors 2 and 4 is increased in peripheral blood and synovial fluid monocytes of patients with enthesitis-related arthritis subtype of juvenile idiopathic arthritis. Rheumatology (Oxford). 50:481–8. DOI: 10.1093/rheumatology/keq362. PMID: 21097451.
Article
29. Viswanath V, Myles A, Dayal R, Aggarwal A. 2011; Levels of serum matrix metalloproteinase-3 correlate with disease activity in the enthesitis-related arthritis category of juvenile idiopathic arthritis. J Rheumatol. 38:2482–7. DOI: 10.3899/jrheum.110352. PMID: 21885500.
Article
30. Syed RH, Gilliam BE, Moore TL. 2008; Rheumatoid factors and anticyclic citrullinated peptide antibodies in pediatric rheumatology. Curr Rheumatol Rep. 10:156–63. DOI: 10.1007/s11926-008-0027-4. PMID: 18460272.
Article
31. Hamooda M, Fouad H, Galal N, Sewelam N, Megahed D. 2016; Anti-cyclic citrullinated peptide antibodies in children with juvenile idiopathic arthritis. Electron Physician. 8:2897–903. DOI: 10.19082/2897. PMID: 27790341. PMCID: PMC5074747.
Article
32. Behrens EM, Beukelman T, Paessler M, Cron RQ. 2007; Occult macrophage activation syndrome in patients with systemic juvenile idiopathic arthritis. J Rheumatol. 34:1133–8. PMID: 17343315.
33. Ravelli A, Grom AA, Behrens EM, Cron RQ. 2012; Macrophage activation syndrome as part of systemic juvenile idiopathic arthritis: diagnosis, genetics, pathophysiology and treatment. Genes Immun. 13:289–98. DOI: 10.1038/gene.2012.3. PMID: 22418018.
Article
34. Ravelli A, Minoia F, Davì S, Horne A, Bovis F, Pistorio A, et al. Paediatric Rheumatology International Trials Organisation. Childhood Arthritis and Rheumatology Research Alliance. Pediatric Rheumatology Collaborative Study Group. Histiocyte Society. 2016; 2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a European league against Rheumatism/American College of Rheumatology/Paediatric Rheumatology International Trials Organisation collaborative initiative. Arthritis Rheumatol. 68:566–76. DOI: 10.1002/art.39332. PMID: 26314788.
35. Moncrieffe H, Ursu S, Holzinger D, Patrick F, Kassoumeri L, Wade A, et al. 2013; A subgroup of juvenile idiopathic arthritis patients who respond well to methotrexate are identified by the serum biomarker MRP8/14 protein. Rheumatology (Oxford). 52:1467–76. DOI: 10.1093/rheumatology/ket152. PMID: 23620557.
Article
36. Anink J, Van Suijlekom-Smit LW, Otten MH, Prince FH, van Rossum MA, Dolman KM, et al. 2015; MRP8/14 serum levels as a predictor of response to starting and stopping anti-TNF treatment in juvenile idiopathic arthritis. Arthritis Res Ther. 17:200. DOI: 10.1186/s13075-015-0723-1. PMID: 26249667. PMCID: PMC4528380.
Article
37. Foell D, Wulffraat N, Wedderburn LR, Wittkowski H, Frosch M, Gerss J, et al. Paediatric Rheumatology International Trials Organization (PRINTO). 2010; Methotrexate withdrawal at 6 vs 12 months in juvenile idiopathic arthritis in remission: a randomized clinical trial. JAMA. 303:1266–73. DOI: 10.1001/jama.2010.375. PMID: 20371785.
38. Gohar F, Anink J, Moncrieffe H, Van Suijlekom-Smit LWA, Prince FHM, van Rossum MAJ, et al. 2018; S100A12 is associated with response to therapy in juvenile idiopathic arthritis. J Rheumatol. 45:547–54. DOI: 10.3899/jrheum.170438. PMID: 29335345. PMCID: PMC5880729.
Article
39. Yamasaki Y, Takei S, Imanaka H, Nerome Y, Kubota T, Nonaka Y, et al. 2016; Prediction of long-term remission of oligo/polyarticular juvenile idiopathic arthritis with S100A12 and vascular endothelial growth factor. Mod Rheumatol. 26:551–6. DOI: 10.3109/14397595.2015.1109784. PMID: 26474088.
Article
40. Gerss J, Roth J, Holzinger D, Ruperto N, Wittkowski H, Frosch M, et al. Paediatric Rheumatology International Trials Organization (PRINTO). 2012; Phagocyte-specific S100 proteins and high-sensitivity C reactive protein as biomarkers for a risk-adapted treatment to maintain remission in juvenile idiopathic arthritis: a comparative study. Ann Rheum Dis. 71:1991–7. DOI: 10.1136/annrheumdis-2012-201329. PMID: 22689317.
Article
41. Vastert S, Prakken B. 2014; Update on research and clinical translation on specific clinical areas: from bench to bedside: how insight in immune pathogenesis can lead to precision medicine of severe juvenile idiopathic arthritis. Best Pract Res Clin Rheumatol. 28:229–46. DOI: 10.1016/j.berh.2014.05.002. PMID: 24974060.
Article
42. Vastert SJ, de Jager W, Noordman BJ, Holzinger D, Kuis W, Prakken BJ, et al. 2014; Effectiveness of first-line treatment with recombinant interleukin-1 receptor antagonist in steroid-naive patients with new-onset systemic juvenile idiopathic arthritis: results of a prospective cohort study. Arthritis Rheumatol. 66:1034–43. DOI: 10.1002/art.38296. PMID: 24757154.
Article
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