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Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis

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Abstract

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression of targeted mRNAs, which are important in the pathogenesis of autoimmune diseases. MiRNAs may have the potential to serve as biomarkers of disease. We evaluated serum levels of selected miRNAs and their associations with disease activity in juvenile idiopathic arthritis (JIA). Sera and peripheral blood leukocytes were collected from patients with JIA (8 systemic onset, 16 polyarthritis) and healthy controls. Levels of miR-16, miR-132, miR-146a, miR-155, and miR-223 were quantified. Levels of miR-223 in sera were significantly higher in patients in the active phase of systemic onset JIA than in controls. MiRNAs of peripheral blood leukocytes did not exhibit any difference between patients with JIA and controls. In both systemic onset JIA and polyarthritis patients, levels of miR-223 and miR-16 correlated with erythrocyte sedimentation rate and matrix metalloproteinase-3, respectively. MiR-146a and miR-223 in polyarthritis showed correlations with matrix metalloproteinase-3. Expressions of miRNAs were altered in patients with JIA. Serum levels of miR-223 may be a potential disease biomarker. Investigation of miRNAs could be helpful in understanding the pathogenesis of JIA and could aid in the identification of additional disease biomarkers.

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References

  1. Ravelli A, Martini A (2007) Juvenile idiopathic arthritis. Lancet 369:767–778

    Article  CAS  PubMed  Google Scholar 

  2. Yokota S, Imagawa T, Mori M, Miyamae T, Aihara Y, Takei S, Iwata N, Umebayashi H, Murata T, Miyoshi M, Tomiita M, Nishimoto N, Kishimoto T (2008) Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 371:998–1006

    Article  CAS  PubMed  Google Scholar 

  3. Horneff G, De Bock F, Foeldvari I, Girschick HJ, Michels H, Moebius D, Schmeling H, German, Austrian Paediatric Rheumatology Collaborative Study G (2009) Safety and efficacy of combination of etanercept and methotrexate compared to treatment with etanercept only in patients with juvenile idiopathic arthritis (JIA): preliminary data from the German JIA Registry. Ann Rheum Dis 68:519–525

    Article  CAS  PubMed  Google Scholar 

  4. De Benedetti F, Brunner HI, Ruperto N, Kenwright A, Wright S, Calvo I, Cuttica R, Ravelli A, Schneider R, Woo P, Wouters C, Xavier R, Zemel L, Baildam E, Burgos-Vargas R, Dolezalova P, Garay SM, Merino R, Joos R, Grom A, Wulffraat N, Zuber Z, Zulian F, Lovell D, Martini A, Printo, Prcsg (2012) Randomized trial of tocilizumab in systemic juvenile idiopathic arthritis. N Engl J Med 367:2385–2395

    Article  PubMed  Google Scholar 

  5. Ferucci ED, Majka DS, Parrish LA, Moroldo MB, Ryan M, Passo M, Thompson SD, Deane KD, Rewers M, Arend WP, Glass DN, Norris JM, Holers VM (2005) Antibodies against cyclic citrullinated peptide are associated with HLA-DR4 in simplex and multiplex polyarticular-onset juvenile rheumatoid arthritis. Arthritis Rheum 52:239–246

    Article  CAS  PubMed  Google Scholar 

  6. De Benedetti F, Massa M, Robbioni P, Ravelli A, Burgio GR, Martini A (1991) Correlation of serum interleukin-6 levels with joint involvement and thrombocytosis in systemic juvenile rheumatoid arthritis. Arthritis Rheum 34:1158–1163

    Article  PubMed  Google Scholar 

  7. De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini A (1994) Serum soluble interleukin 6 (IL-6) receptor and IL-6/soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 93:2114–2119

    Article  PubMed Central  PubMed  Google Scholar 

  8. Maeno N, Takei S, Nomura Y, Imanaka H, Hokonohara M, Miyata K (2002) 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 46:2539–2541, author reply 41–2

    Article  PubMed  Google Scholar 

  9. Lin YT, Wang CT, Gershwin ME, Chiang BL (2011) The pathogenesis of oligoarticular/polyarticular vs systemic juvenile idiopathic arthritis. Autoimmun Rev 10:482–489

    Article  CAS  PubMed  Google Scholar 

  10. Foell D, Wittkowski H, Hammerschmidt I, Wulffraat N, Schmeling H, Frosch M, Horneff G, Kuis W, Sorg C, Roth J (2004) Monitoring neutrophil activation in juvenile rheumatoid arthritis by S100A12 serum concentrations. Arthritis Rheum 50:1286–1295

    Article  CAS  PubMed  Google Scholar 

  11. Frosch M, Vogl T, Seeliger S, Wulffraat N, Kuis W, Viemann D, Foell D, Sorg C, Sunderkotter C, Roth J (2003) Expression of myeloid-related proteins 8 and 14 in systemic-onset juvenile rheumatoid arthritis. Arthritis Rheum 48:2622–2626

    Article  CAS  PubMed  Google Scholar 

  12. Ruvkun G (2001) Molecular biology. Glimpses of a tiny RNA world. Science 294:797–799

    Article  CAS  PubMed  Google Scholar 

  13. Filipowicz W, Bhattacharyya SN, Sonenberg N (2008) Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet 9:102–114

    Article  CAS  PubMed  Google Scholar 

  14. Mendell JT, Olson EN (2012) MicroRNAs in stress signaling and human disease. Cell 148:1172–1187

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. O'Connell RM, Rao DS, Baltimore D (2012) microRNA regulation of inflammatory responses. Annu Rev Immunol 30:295–312

    Article  PubMed  Google Scholar 

  16. Chen X, Ba Y, Ma L, Cai X, Yin Y, Wang K, Guo J, Zhang Y, Chen J, Guo X, Li Q, Li X, Wang W, Zhang Y, Wang J, Jiang X, Xiang Y, Xu C, Zheng P, Zhang J, Li R, Zhang H, Shang X, Gong T, Ning G, Wang J, Zen K, Zhang J, Zhang CY (2008) Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res 18:997–1006

    Article  CAS  PubMed  Google Scholar 

  17. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, Peterson A, Noteboom J, O'Briant KC, Allen A, Lin DW, Urban N, Drescher CW, Knudsen BS, Stirewalt DL, Gentleman R, Vessella RL, Nelson PS, Martin DB, Tewari M (2008) Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A 105:10513–10518

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Luo X, Tsai LM, Shen N, Yu D (2010) Evidence for microRNA-mediated regulation in rheumatic diseases. Ann Rheum Dis 69(Suppl 1):i30–i36

    Article  CAS  PubMed  Google Scholar 

  19. Alevizos I, Illei GG (2010) MicroRNAs as biomarkers in rheumatic diseases. Nat Rev Rheumatol 6:391–398

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Ceribelli A, Yao B, Dominguez-Gutierrez PR, Nahid MA, Satoh M, Chan EK (2011) MicroRNAs in systemic rheumatic diseases. Arthritis Res Ther 13:229

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Duroux-Richard I, Jorgensen C, Apparailly F (2012) What do microRNAs mean for rheumatoid arthritis? Arthritis Rheum 64:11–20

    Article  CAS  PubMed  Google Scholar 

  22. Stanczyk J, Pedrioli DM, Brentano F, Sanchez-Pernaute O, Kolling C, Gay RE, Detmar M, Gay S, Kyburz D (2008) Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum 58:1001–1009

    Article  PubMed  Google Scholar 

  23. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK (2008) Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther 10:R101

    Article  PubMed Central  PubMed  Google Scholar 

  24. Filkova M, Aradi B, Senolt L, Ospelt C, Vettori S, Mann H, Filer A, Raza K, Buckley CD, Snow M, Vencovsky J, Pavelka K, Michel BA, Gay RE, Gay S, Jungel A (2014) Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. Ann Rheum Dis 73:1898–1904

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Hastings ML, Palma J, Duelli DM (2012) Sensitive PCR-based quantitation of cell-free circulating microRNAs. Methods 58:144–150

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Kawano Y, Iwata S, Kawada J, Gotoh K, Suzuki M, Torii Y, Kojima S, Kimura H, Ito Y (2013) Plasma viral microRNA profiles reveal potential biomarkers for chronic active Epstein-Barr virus infection. J Infect Dis 208:771–779

    Article  CAS  PubMed  Google Scholar 

  27. Chen CZ, Li L, Lodish HF, Bartel DP (2004) MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86

    Article  CAS  PubMed  Google Scholar 

  28. Li YT, Chen SY, Wang CR, Liu MF, Lin CC, Jou IM, Shiau AL, Wu CL (2012) Brief report: amelioration of collagen-induced arthritis in mice by lentivirus-mediated silencing of microRNA-223. Arthritis Rheum 64:3240–3245

    Article  CAS  PubMed  Google Scholar 

  29. Kurowska-Stolarska M, Alivernini S, Ballantine LE, Asquith DL, Millar NL, Gilchrist DS, Reilly J, Ierna M, Fraser AR, Stolarski B, McSharry C, Hueber AJ, Baxter D, Hunter J, Gay S, Liew FY, McInnes IB (2011) MicroRNA-155 as a proinflammatory regulator in clinical and experimental arthritis. Proc Natl Acad Sci U S A 108:11193–11198

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Murata K, Yoshitomi H, Tanida S, Ishikawa M, Nishitani K, Ito H, Nakamura T (2010) Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther 12:R86

    Article  PubMed Central  PubMed  Google Scholar 

  31. Sugatani T, Hruska KA (2009) Impaired micro-RNA pathways diminish osteoclast differentiation and function. J Biol Chem 284:4667–4678

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  32. Taganov KD, Boldin MP, Chang KJ, Baltimore D (2006) NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci U S A 103:12481–12486

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  33. Chan EK, Ceribelli A, Satoh M (2013) MicroRNA-146a in autoimmunity and innate immune responses. Ann Rheum Dis 72(2):i90-5

    Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan

    Yasuko Kamiya, Jun-ichi Kawada, Yoshihiko Kawano, Yuka Torii & Yoshinori Ito

  2. Department of Infection and Immunology, Aichi Children’s Health and Medical Center, 1-2 Osakada Morioka-cho, Obu, Aichi, 474-8710, Japan

    Shinji Kawabe & Naomi Iwata

Authors
  1. Yasuko Kamiya
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  2. Jun-ichi Kawada
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  3. Yoshihiko Kawano
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  4. Yuka Torii
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  6. Naomi Iwata
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  7. Yoshinori Ito
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Correspondence to Yoshinori Ito.

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Kamiya, Y., Kawada, Ji., Kawano, Y. et al. Serum microRNAs as Potential Biomarkers of Juvenile Idiopathic Arthritis. Clin Rheumatol 34, 1705–1712 (2015). https://doi.org/10.1007/s10067-015-2922-1

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  • DOI: https://doi.org/10.1007/s10067-015-2922-1

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