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Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis

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Abstract

YKL-40, also known as human cartilage glycoprotein 39, is a member of the “mammalian chitinase-like proteins” family without chitinase activity. Increased serum concentrations are associated with inflammatory processes and several types of cancer. In this study, we evaluated YKL-40 levels in serum and synovial fluid of patients with rheumatoid arthritis in comparison with the ultrasonographic findings. YKL-40 levels were measured by enzyme-linked immunosorbent assay in 25 patients with active rheumatoid arthritis and in 40 healthy subjects. B mode and power Doppler were performed to determine synovial thickening and vascularization. Serum YKL-40 level in patients was significantly higher than the concentration in healthy controls (P < 0.01). In patients with rheumatoid arthritis, the level of the glycoprotein in synovial fluid was remarkably elevated compared to the serum level (P = 0.003). The B mode and power Doppler scores correlated to YKL-40 in serum and synovial fluid (P = 0.07). Serum YKL-40 levels were related positively to serum markers of inflammation such as C-reactive protein (P = 0.004) and erythrocyte sedimentation rate (P = 0.003). This study is the first to demonstrate a relationship between YKL-40 levels and ultrasonographic examinations in Bulgarian patients with rheumatoid arthritis. The findings suggest that YKL-40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation.

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References

  1. Johansen JS (2006) Studies on serum YKL-40 as a biomarker in diseases with inflammation, tissue remodelling, fibroses and cancer. Dan Med Bull 53:172–209

    PubMed  CAS  Google Scholar 

  2. Rehli M, Krause SW, Andreesen R (1997) Molecular characterization of the gene for human cartilage gp-39 (CHI3L1), a member of the chitinase protein family and marker for late stages of macrophage differentiation. Genomics 43:221–225

    Article  PubMed  CAS  Google Scholar 

  3. Roslind A, Johansen JS (2009) YKL-40: a novel marker shared by chronic inflammation and oncogenic transformation. Methods Mol Biol 511:159–184

    Article  PubMed  CAS  Google Scholar 

  4. Bojesen SE, Johansen JS, Nostegaard BG (2011) Plasma YKL-40 levels in healthy subjects from the general population. Clin Chim Acta 412:709–712

    Article  PubMed  CAS  Google Scholar 

  5. Güngen G, Ardic F, Fιndıkoğlu G, Rota S (2011) The effect of mud pack therapy on serum YKL-40 and hsCRP levels in patients with knee osteoarthritis. Rheumatol Int 31:1–10

    Article  Google Scholar 

  6. Zyvanovic S, Rackov LP, Vojvodic D, Vucetic D (2009) Human cartilage glycoprotein 39-biomarker of joint damage in knee osteoarthritis. Int Orthop 33:1165–1170

    Article  Google Scholar 

  7. Michelsen AE, Rathcke CN, Skjelland M, Holm S, Ranheim T, Krohg-Sørensen K, Klingvall MF, Brosstad F, Oie E, Vestergaard H, Aukrust P, Halvorsen B (2010) Increased YKL-40 expression in patients with carotid atherosclerosis. Atherosclerosis 211:589–595

    Article  PubMed  CAS  Google Scholar 

  8. Letuve S, Kozhich A, Arouche N, Grandsaigne M, Reed J, Dombret MC, Kiener PA, Aubier M, Coyle AJ, Pretolani M (2008) YKL-40 is elevated in patients with chronic obstructive pulmonary disease and activates alveolar macrophages. J Immunol 181:5167–5173

    PubMed  CAS  Google Scholar 

  9. Rondbjerg A, Omerovic E, Vestergaard H (2011) YKL-40 levels are independently associated with albuminuria in type 2. Cardiovasc Diabetol 10:54. doi:10.1186/1475-2840-10-54

    Article  PubMed  Google Scholar 

  10. Cintin C, Johansen JS, Christensen IJ, Price PA, Sørensen S, Nielsen HJ (2002) High serum YKL-40 level after surgery for colorectal carcinoma is related to short survival. Cancer 95:267–274

    Article  PubMed  Google Scholar 

  11. Yamac D, Ozturk B, Coskun U, Tekin E, Sancak B, Yildiz R, Atalay C (2008) Serum YKL-40 levels as a prognostic factor in patients with locally advanced breast cancer. Adv Ther 25:801–809. doi:10.1007/s12325-008-0082-2

    Article  PubMed  Google Scholar 

  12. Hogdall E, Johansen JS (2009) YKL-40 tissue expression and plasma levels in patients with ovarian cancer. Biomed Central Cancer 9:8. doi:10.1186/1471-2407-9-8

    PubMed  Google Scholar 

  13. Kucur M, Isman FK, Balci C, Onal B, Hacibekiroglu M, Ozkan F, Ozkan A (2008) Serum YKL-40 levels and chitotriosidase activity as potential biomarkers in primary prostate cancer and benign prostatic hyperplasia. Urol Oncol 26:47–52

    Article  PubMed  CAS  Google Scholar 

  14. Tanwar MK, Gilbert MR, Holland EC (2002) Gene expression microarray analysis reveals YKL-40 to be a potential serum marker for malignant character in human glioma. Cancer Res 62:4364–4368

    PubMed  CAS  Google Scholar 

  15. Peltomaa R, Paimela L, Harvey S, Helve T, Leirisalo-Repo M (2001) Increased level of YKL-40 in sera from patients with early rheumatoid arthritis: a new biomarker for disease activity. Rheumatol Int 20:192–196

    Article  PubMed  CAS  Google Scholar 

  16. Mandl P, Naredo E, Wakefield RG, Conaghan PG, D’agostino MA, OMERACT Ultrasound Task Force (2011) A systematic literature review analysis of ultrasound joint count and scoring systems to assess synovitis in rheumatoid arthritis according to the OMERACT filter. J Rheumatol 38:2055–2062

    Article  PubMed  Google Scholar 

  17. Schmidt WA, Schmidt H, Schicke B, Cromlica-Ichle E (2004) Standard reference values for musculoskeletal ultrasonography. Ann Rheum Dis 63:988–994

    Article  PubMed  CAS  Google Scholar 

  18. Wakefield RJ, Gibbon WW, Conaghan PG, O’Connor P, McGonagle D, Pease C, Green MJ, Veale DJ, Isaacs JD, Emery P (2000) The value of sonography in the detection of bone erosions in patients with rheumatoid arthritis: a comparison with conventional radiography. Arthritis Rheum 43:2762–2770

    Article  PubMed  CAS  Google Scholar 

  19. Naredo E, Bonilla G, Gamero F (2005) Assessment of inflammatory activity in rheumatoid arthritis: a comparative study of clinical avaluation with grey scale and power Doppler ultrasonography. Ann Rheum Dis 64:375–381

    Article  PubMed  CAS  Google Scholar 

  20. Fox DA (1997) The role of T cells in the immunopathogenesis of rheumatoid arthritis. New perspectives. Arthritis Rheum 40:598–609

    Article  PubMed  CAS  Google Scholar 

  21. Emery P, Gough A, Salmon M, Devlin J (1993) Medical management of rheumatoid arthritis. BMJ 307:425–428

    Article  Google Scholar 

  22. Kirwan JR, Arthritis and Rheumatism Council Low-Dose Glucocorticoid Study Group (1995) The effect of glucocorticoids on joint destruction in rheumatoid arthritis. N Engl J Med 333:142–147

    Article  PubMed  CAS  Google Scholar 

  23. Johansen JS, Jensen HS, Price PA (1993) A new biochemical marker for joint injury. Analysis of YKL-40 in serum and synovial fluid. Br J Rheumatol 32:949–955

    Article  PubMed  CAS  Google Scholar 

  24. Volck B, Johansen JS, Stoltenberg M, Garbarsch C, Price PA, Østergaard M, Østergaard K, Løvgreen-Nielsen P, Sonne-Holm S, Lorenzen I (2001) Studies on YKL-40 in knee joints of patients with rheumatoid arthritis and osteoarthritis. Involvement of YKL-40 in the joint pathology. Osteoarthr Cartil 9:203–214

    Article  PubMed  CAS  Google Scholar 

  25. Knudsen LS, Hetland ML, Johansen JS, Skjodt H, Peters ND, Colic A, Grau K, Nielsen NJ, Ostergaard M (2009) Changes in plasma IL-6, plasma VEGF and serum YKL-40 during treatment with etanercept and methotrexate or etanercept alone in patients with active rheumatoid arthritis despite methotrexate therapy. Biomarker Insights 4:91–95

    PubMed  CAS  Google Scholar 

  26. Kirkpatrick RB, Emery JG, Connor JR, Dodds R, Lysko PG, Rosenberg M (1997) Induction and expression of human cartilage glycoprotein 39 in rheumatoid inflammatory and peripheral blood monocyte-derived macrophages. Exp Cell Res 237:46–54

    Article  PubMed  CAS  Google Scholar 

  27. Volck B, Price PA, Johansen JS, Sørensen O, Benfield T, Calafat J, Nielsen HJ, Borregaard N (1998) YKL-40, a mammalian member of the bacterial chitinase family, is a matrix protein of specific granules in human neutrophils. Proc Assoc Am Phys 110:351–360

    PubMed  CAS  Google Scholar 

  28. Hakala BE, White C, Recklies AD (1993) Human cartilage gp-39, a major secretory product of articular chondrocytes and synovial cells, is a mammalian member of a chitinase protein family. J Biol Chem 268:25803–25810

    PubMed  CAS  Google Scholar 

  29. Takahashi M, Naito K, Abe M, Sawada T, Nagano A (2004) Relationship between radiographic grading of osteoarthritis and the biochemical markers for arthritis in knee osteoarthritis. Arthritis Res Ther 6:208–212

    Article  Google Scholar 

  30. Syversen SW, Goll GL, Heijde D, Landeve R, Lie BA, Odegard S, Uhlig T, Gaarder PI, Kvien TK (2009) Prediction of radiographic progression in rheumatoid arthritis and the role of antibodies against mutated citrullinated vimentin: results from a 10-year prospective study. Ann Rheum Dis 69:345–351. doi:10.1136/ard.2009.113092

    Article  PubMed  Google Scholar 

  31. Weidekamm C, Koller M, Weber M, Kainberger F (2003) Diagnostic value of high-resolution B-mode and Doppler sonography for imaging of hand and finger joints in rheumatoid arthritis. Arthritis Rheum 48:325–333

    Article  PubMed  CAS  Google Scholar 

  32. Francescone RA, Scully S, Faibish M, Taylor SL, Oh D, Moral L, Yan W, Bentley B, Shao R (2011) Role of YKL-40 in the angiogenesis, radioresistance, and progression of glioblastoma. J Biol Chem 286:15332–15343

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The study was supported by grants no. 1/2009 and 1/2010 from Medical University-Plovdiv.

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Authors and Affiliations

  1. Department of Medical Biology, Medical University-Plovdiv, 15A V. Aprilov Blvd, 4002, Plovdiv, Bulgaria

    Maria Kazakova & Victoria Sarafian

  2. Department of Rheumatology, Medical University-Plovdiv, 15A V. Aprilov Blvd, 4002, Plovdiv, Bulgaria

    Anastas Batalov

  3. Department of Clinical Laboratory, Medical University-Plovdiv, 15A V. Aprilov Blvd, 4002, Plovdiv, Bulgaria

    Tanya Deneva

  4. Department of Health Management, Health Economics and General Medicine, Medical University-Plovdiv, 15A V. Aprilov Blvd, 4002, Plovdiv, Bulgaria

    Nonka Mateva

  5. Clinic of Rheumatology, Medical University-Sofia, 13 Urvich Str, 1612, Sofia, Bulgaria

    Zlatimir Kolarov

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  1. Maria Kazakova
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  2. Anastas Batalov
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  3. Tanya Deneva
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  4. Nonka Mateva
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Correspondence to Victoria Sarafian.

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Kazakova, M., Batalov, A., Deneva, T. et al. Relationship between sonographic parameters and YKL-40 levels in rheumatoid arthritis. Rheumatol Int 33, 341–346 (2013). https://doi.org/10.1007/s00296-012-2387-3

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  • DOI: https://doi.org/10.1007/s00296-012-2387-3

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