Biomarkers in Spondyloarthropathies

  • Chun-Hsiung Chen
  • David Tak Yan Yu
  • Chung-Tei Chou
Part of the Advances in Experimental Medicine and Biology book series (volume 649)

Abstract

The study of biomarkers in spondyloarthropathy (SpA) has emerged to be a very important field of research. This is particularly because the two commonly used biomarkers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), are of very low sensitivity and specificity. The second reason is, with advances in the treatment of SpA by the very expensive tumor necrosis factor-α (TNF-α) blockers, for cost-effectiveness, clinicians need to be much more accurate in predicting disease progression, evaluating disease activity and monitoring therapeutic efficacy. This review focuses on several biomarkers of promise: matrix metalloproteinases 3 (MMP-3), Type II collagen neoepitope (C2C and C1-2C), C-propeptide of Type II collagen (CPII), aggrecan 846 epitope, macrophage colony stimulating factor (M-CSF), serum amyloid A (SAA) and Interleukin-6 (IL-6). The results summarized in Table 1 call for a co-ordinated effort for systematic studies of existing biomarkers and for search for new candidates.

Keywords

Placebo Arthritis Sedimentation Osteoarthritis Peri 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Zochling J Brandt J, Braun J. The current concept of spondyloarthritis with special emphasis on undifferentiated spondyloarthritis. Rheumatology (Oxford) 2005; 44:1483–91.CrossRefGoogle Scholar
  2. 2.
    Garrett S, Jenkinson T, Kennedy LG et al. A new approach to defining disease status in ankylosing spondylitis: the bath ankylosing spondylitis disease activity index. J Rheumatol 1994; 21:2286–91.PubMedGoogle Scholar
  3. 3.
    Braun J, Pham T, Sieper J et al. International ASAS consensus statement for the use of anti-tumour necrosis factor agents in patients with ankylosing spondylitis. Ann Rheum Dis 2003; 62:817–824.PubMedCrossRefGoogle Scholar
  4. 4.
    Sheehan NJ, Slavin BM, Donovan MP et al. Lack of correlation between clinical disease activity and erythrocyte sedimentation rate, acute phase proteins or protease inhibitors in ankylosing spondylitis. Br J Rheumatol 1986; 25:171–4.PubMedCrossRefGoogle Scholar
  5. 5.
    Ruof J, Stucki G. Validity aspects of erythrocyte sedimentation rate and C-reactive protein in ankylosing spondylitis: a literature review. J Rheumatol 1999; 26:966–70.PubMedGoogle Scholar
  6. 6.
    Gorman JD, Sack KE, Davis JC Jr. Treatment of ankylosing spondylitis by inhibition of tumor necrosis factor alpha. N Engl J Med 2002; 346:1349–56.PubMedCrossRefGoogle Scholar
  7. 7.
    Braun J, Brandt J, Listing J et al. Treatment of active ankylosing spondylitis with infliximab: A randomised controlled multicentre trial. Lancet 2002; 359:1187–93.PubMedCrossRefGoogle Scholar
  8. 8.
    Bauer DC, Hunter DJ, Abramson SB et al. Osteoarthritis biomarkers network. Classification of osteoarthritis biomarkers: a proposed approach. Osteoarthritis Cartilage 2006; 14:723–7.PubMedCrossRefGoogle Scholar
  9. 9.
    Huang F, Zhu J, Zhang L et al. Response to one infusion predicts subsequent improvement as well as the rate of relapse of ankylosing spondylitis infused with three pulses of infliximab. Clin Rheumatol 2007; 26:920–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Kruithof E, De Rycke L, Vandooren B et al. Identification of synovial biomarkers of response to experimental treatment in early-phase clinical trials in spondylarthritis. Arthritis Rheum 2006; 54:1795–804.PubMedCrossRefGoogle Scholar
  11. 11.
    Pepe MS, Janes H, Longton G et al. Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker. Am J Epidemiol 2004; 159:882–90.PubMedCrossRefGoogle Scholar
  12. 12.
    Nagase H, Woessner JF Jr. Matrix metalloproteinases. J Biol Chem 1999; 274:21491–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Ishiguro N, Ito T, Miyazaki K et al. Matrix metalloproteinases, tissue inhibitors of metalloproteinases and glycosaminoglycans in synovial fluid from patients with rheumatoid arthritis. J Rheumatol 1999; 26:34–40.PubMedGoogle Scholar
  14. 14.
    Ishiguro N, Ito T, Obata K et al. Determination of stromelysin-1,72 and 92 kDa type IV collagenase, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in synovial fluid and serum from patients with rheumatoid arthritis. J Rheumatol 1996; 23:1599–604.PubMedGoogle Scholar
  15. 15.
    Yoshihara Y, Nakamura H, Obata K et al. Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 2000; 59:455–61.PubMedCrossRefGoogle Scholar
  16. 16.
    Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function and biochemistry. Circ Res 2003; 92:827–39.PubMedCrossRefGoogle Scholar
  17. 17.
    Grillet B, Dequeker J, Paemen L et al. Gelatinase B in chronic synovitis: immunolocalization with a monoclonal antibody. Br J Rheumatol 1997; 36:744–7.PubMedCrossRefGoogle Scholar
  18. 18.
    Hembry RM, Bagga MR, Reynolds JJ et al. Immunolocalisation studies on six matrix metalloproteinases and their inhibitors, TIMP-1 and TIMP-2, in synovia from patients with osteo-and rheuatoid arthritis. Ann Rheum Dis 1995; 54:25–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Okada Y, Takeuchi N, Tomita K et al. Immunolocalization of matrix metalloproteinase 3 (stromelysin) in rheumatoid synovioblasts (B-cells): Correlation with rheumatoid arthritis. Ann Rheum Dis 1989; 48:645–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Ahrens D, Koch AE, Pope RM et al. Expression of matrix metalloproteinase 9 (96-kd gelatinase B) in human rheumatoid arthritis. Arthritis Rheum 1996; 39:1576–87.PubMedCrossRefGoogle Scholar
  21. 21.
    Cole AA, Chubinskaya S, Schumacher B et al. Chondrocyte matrix metalloproteinase-8. Human articular chondrocytes express neutrophil collagenase. J Biol Chem 1996; 271:11023–6.PubMedCrossRefGoogle Scholar
  22. 22.
    Mohtai M, Smith RL, Schurman DJ et al. Expression of 92-kD type IV collagenase/gelatinase (gelatinase B) in osteoarthritic cartilage and its induction in normal human articular cartilage by interleukin 1. J Clin Invest 1993; 92:179–85.PubMedCrossRefGoogle Scholar
  23. 23.
    MacNaul KL, Chartrain N, Lark M et al. Discoordinate expression of stromelysin, collagenase and tissue inhibitor of metalloproteinases-1 in rheumatoid human synovial fibroblasts. Synergistic effects of interleukin-1 and tumor necrosis factor-alpha on stromelysin expression. J Biol Chem 1990; 265:17238–45.PubMedGoogle Scholar
  24. 24.
    Zhang Y, McCluskey K, Fujii K et al. Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-alpha, granulocyte-macrophage, CSF and IL-1 beta through prostaglandin-dependent and independent mechanisms. J Immunol 1998; 161:3071–6.PubMedGoogle Scholar
  25. 25.
    Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function and biochemistry. Circ Res 2003; 92:827–839.PubMedCrossRefGoogle Scholar
  26. 26.
    Manicourt DH, Fujimoto N, Obata K et al. Levels of circulating collagenase, stromelysin-1 and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum levels of antigenic keratan sulfate and systemic parameters of inflammation. Arthritis Rheum 1995; 38:1031–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Manicourt DH, Fujimoto N, Obata K et al. Serum levels of collagenase, stromelysin-1 and TIMP-1. Age-and sex-related differences in normal subjects and relationship to the extent of joint involvement and serum levels of antigenic keratan sulfate in patients with osteoarthritis. Arthritis Rheum 1994; 37:1774–83.PubMedCrossRefGoogle Scholar
  28. 28.
    Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem 1997; 378:151–60.PubMedGoogle Scholar
  29. 29.
    Vandooren B, Kruithof E, Yu DT et al. Involvement of matrix metalloproteinases and their inhibitors in peripheral synovitis and down-regulation by tumor necrosis factor alpha blockade in spondylarthropathy. Arthritis Rheum 2004; 50:2942–2953.PubMedCrossRefGoogle Scholar
  30. 30.
    Chen CH, Lin KC, Yu DT et al. Serum matrix metalloproteinases and tissue inhibitors of metalloproteinases in ankylosing spondylitis: MMP-3 is a reproducibly sensitive and specific biomarker of disease activity. Rheumatology (Oxford) 2006; 45:414–20.CrossRefGoogle Scholar
  31. 31.
    Chen CH, Liao HT, Chen HA et al. Serum levels of matrix metalloproteinase-3 in undifferentiated spondyloarthropathy. Scand J Rheumatol 2007; 36:326–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Yang C, Gu J, Rihl M et al. Serum levels of matrix metalloproteinase 3 and macrophage colony-stimulating factor 1 correlate with disease activity in ankylosing spondylitis. Arthritis Rheum 2004; 51:691–699.PubMedCrossRefGoogle Scholar
  33. 33.
    Maksymowych WP, Poole AR, Hiebert L et al. Etanercept exerts beneficial effects on articular cartilage biomarkers of degradation and turnover in patients with ankylosing spondylitis. J Rheumatol 2005; 32:1911–1917.PubMedGoogle Scholar
  34. 34.
    Maksymowych WP, Jhangri GS, Lambert RG et al. Infliximab in ankylosing spondylitis: A prospective observational inception cohort analysis of efficacy and safety. J Rheumatol 2002; 29:959–965.PubMedGoogle Scholar
  35. 35.
    Woo JH, Lee HJ, Sung IH et al. Changes of clinical response and bone biochemical markers in patients with ankylosing spondylitis taking etanercept. J Rheumatol; in press.Google Scholar
  36. 36.
    Maksymowych WP, Landewe R, Conner-Spady B et al. Serum matrix metalloproteinase 3 is an independent predictor of structural damage progression in patients with ankylosing spondylitis. Arthritis Rheum 2007; 56:1846–53.PubMedCrossRefGoogle Scholar
  37. 37.
    Creemers MC, Franssen MJ, van’t Hof MA et al. Assessment of outcome in ankylosing spondylitis: An extended radiographic scoring system. Ann Rheum Dis 2005; 64:127–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Rousseau JC, Delmas PD. Biological markers in osteoarthritis. Nat Clin Pract Rheumatol 2007; 3:346–56.PubMedCrossRefGoogle Scholar
  39. 39.
    Billinghurst RC, Dahlberg L, Ionescu M et al. Enhanced cleavage of type II collagen by collagenases in osteoarthritic articular cartilage. J Clin Invest 1997; 99:1534–45.PubMedCrossRefGoogle Scholar
  40. 40.
    Kojima T, Mwale F, Yasuda T et al. Early degradation of type IX and type II collagen with the onset of experimental inflammatory arthritis. Arthritis Rheum 2001; 44:120–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Nelson F, Dahlberg L, Laverty S et al. Evidence for altered synthesis of type II collagen in patients with osteoarthritis. J Clin Invest 1998; 102:2115–25.PubMedCrossRefGoogle Scholar
  42. 42.
    Poole AR. Cartilage in health and disease. In: Koopman W, ed. Arthritis and Allied Conditions: A Textbook of Rheumatology. 14th ed. Philadelphia: Lippincott, Williams and Wilkins, 2001; 226–84.Google Scholar
  43. 43.
    Poole AR, Howell DS. Etiopathogenesis of osteoarthritis. In: Moskowitz RV, Howell DS, Goldberg VM, Mankin HJ, eds. Osteoarthritis: Diagnosis and Management. 3rd ed. Baltimore: Saunders, 2001; 29–47.Google Scholar
  44. 44.
    Kim TH, Stone M, Payne U et al. Cartilage biomarkers in ankylosing spondylitis: relationship to clinical variables and treatment response. Arthritis Rheum 2005; 52:885–91.PubMedCrossRefGoogle Scholar
  45. 45.
    Braun J, Bollow M, Neure L et al. Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis. Arthritis Rheum 1995; 38:499–505.PubMedCrossRefGoogle Scholar
  46. 46.
    François RJ, Neure L, Sieper J et al. Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases. Ann Rheum Dis 2006; 65:713–20.PubMedCrossRefGoogle Scholar
  47. 47.
    Yang PT, Kasai H, Xiao WG et al. Increased expression of macrophage colony-stimulating factor in ankylosing spondylitis and rheumatoid arthritis. Ann Rheum Dis 2006; 65:1671–2.PubMedCrossRefGoogle Scholar
  48. 48.
    Uhlar CM, Whitehead AS. Serum amyloid A, the major vertebrate acute-phase reactant. Eur J Biochem 1999; 265:501–23.PubMedCrossRefGoogle Scholar
  49. 49.
    O’Hara R, Murphy EP, Whitehead AS et al. Acute-phase serum amyloid a production by rheumatoid arthritis synovial tissue. Arthritis Res 2000; 2:142–4.PubMedCrossRefGoogle Scholar
  50. 50.
    Vallon R, Freuler F, Desta-Tsedu N et al. Serum amyloid a (apoSAA) expression is up-regulated in rheumatoid arthritis and induces transcription of matrix metalloproteinases. J Immunol 2001; 166:2801–7.PubMedGoogle Scholar
  51. 51.
    Strissel KJ, Girard MT, West-Mays JA et al. Role of serum amyloid A as an intermediate in the IL-1 and PMA-stimulated signaling pathways regulating expression of rabbit fibroblast collagenase. Exp Cell Res 1997; 237:275–87.PubMedCrossRefGoogle Scholar
  52. 52.
    Dowton SB, Peters CN, Jestus JJ. Regulation of serum amyloid a gene expression in syrian hamsters by cytokines. Inflammation 1991; 15:391–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Migita K, Kawabe Y, Tominaga M et al. Serum amyloid a protein induces production of matrix metalloproteinases by human synovial fibroblasts. Lab Invest 1998; 78:535–9.PubMedGoogle Scholar
  54. 54.
    O’Hara R, Murphy EP, Whitehead AS et al. Local expression of the serum amyloid a and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis. Arthritis Rheum 2004; 50:1788–99.PubMedCrossRefGoogle Scholar
  55. 55.
    Jung SY, Park MC, Park YB et al. Serum amyloid a as a useful indicator of disease activity in patients with ankylosing spondylitis. Yonsei Med J 2007; 48:218–24.PubMedCrossRefGoogle Scholar
  56. 56.
    Lange U, Boss B, Teichmann J et al. Serum amyloid A—An indicator of inflammation in ankylosing spondylitis. Rheumatol Int 2000; 19:119–22.PubMedCrossRefGoogle Scholar
  57. 57.
    Gratacós J, Collado A, Filella X et al. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: A close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol 1994; 33:927–31.PubMedCrossRefGoogle Scholar
  58. 58.
    Bal A, Unlu E, Bahar G et al. Comparisonoof serum IL-1 beta, sIL-2R, IL-6 and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol 2007; 26:211–5.PubMedCrossRefGoogle Scholar
  59. 59.
    Gratacos J, Collado A, Pons F et al. Significant loss of bone mass in patients with early, active ankylosing spondylitis: a followup study. Arthritis Rheum 1999; 42:2319–24.PubMedCrossRefGoogle Scholar
  60. 60.
    Visvanathan S, Wagner CL, Marini JC et al. Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab. Ann Rheum Dis in press.Google Scholar
  61. 61.
    Falkenbach A, Herold M. In ankylosing spondylitis serum interleukin-6 correlates with the degree of mobility restriction, but not with short-term changes in the variables for mobility. Rheumatol Int 1998; 18:103–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Brandt J, Haibel H, Cornely D et al. Successful treatment of active ankylosing spondylitis with the anti-tumor necrosis factor alpha monoclonal antibody infliximab. Arthritis Rheum 2000; 43:1346–52.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2009

Authors and Affiliations

  • Chun-Hsiung Chen
    • 1
  • David Tak Yan Yu
    • 2
  • Chung-Tei Chou
    • 3
  1. 1.Institute of Clinical MedicineNational Yang-Ming University and Veterans General HospitalTaipeiTaiwan
  2. 2.Rheumatology Division Rehabilitation CenterUniversity of CaliforniaLos AngelesUSA
  3. 3.Division of Allergy, Immunology and RheumatologyVeterans General HospitalTaipeiTaiwan

Personalised recommendations