Skip to main content
SpringerLink
Log in

Biomarkers of Fibrosis

  • Chapter
  • First Online:
Scleroderma

  • 1645 Accesses

Abstract

Biomarkers are modern diagnostics that can guide the treatment of our patients in daily clinical life and direct drug development in preclinical and clinical studies. Biological markers allow screening for diseases, giving prognostic information, and assessing disease activity. Over the last 20 years, biomarkers helped to prioritize drug development and minimize risks for drug attrition in late-phase clinical studies. Despite their central roles in modern medicine, the numbers of disease-specific biomarkers that we routinely assess in our patients with systemic sclerosis (SSc) are limited. So far, past medical history, clinical examination, and equipment-based diagnostics (e.g., computed tomography, body plethysmography, and right-heart catheterization studies) dominate our treatment decisions in SSc.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

References

  1. Frank R, Hargreaves R. Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov. 2003;2(7):566–80.

    Article  PubMed  CAS  Google Scholar 

  2. Castro SV, Jimenez SA. Biomarkers in systemic sclerosis. Biomark Med. 2010;4(1):133–47.

    Article  PubMed  CAS  Google Scholar 

  3. Doran JP, Veale DJ. Biomarkers in systemic sclerosis. Rheumatology (Oxford). 2008;47(Suppl 5):v36–8.

    Article  CAS  Google Scholar 

  4. Biomarkers Definitions Working Group. Biomarkers and surrogate endpoints: preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.

    Article  Google Scholar 

  5. Institute NC. Proteomics and cancer. 2011. www.cancer.gov. Accessed 22 Feb 2011.

  6. Kallenberg CG. Anti-centromere antibodies (ACA). Clin Rheumatol. 1990;9(1 Suppl 1):136–9.

    Article  PubMed  CAS  Google Scholar 

  7. Hu PQ, Fertig N, Medsger Jr TA, et al. Correlation of serum anti-DNA topoisomerase I antibody levels with disease severity and activity in systemic sclerosis. Arthritis Rheum. 2003;48(5):1363–73.

    Article  PubMed  CAS  Google Scholar 

  8. Reveille JD, Solomon DH. Evidence-based guidelines for the use of immunologic tests: anticentromere, Scl-70, and nucleolar antibodies. Arthritis Rheum. 2003;49(3):399–412.

    Article  PubMed  Google Scholar 

  9. Aggarwal R, Lucas M, Fertig N, et al. Anti-U3 RNP autoantibodies in systemic sclerosis. Arthritis Rheum. 2009;60(4):1112–8.

    Article  PubMed  Google Scholar 

  10. Sacks DG, Okano Y, Steen VD, et al. Isolated pulmonary hypertension in systemic sclerosis with diffuse cutaneous involvement: association with serum anti-U3RNP antibody. J Rheumatol. 1996;23(4):639–42.

    PubMed  CAS  Google Scholar 

  11. Khanna D, Lovell DJ, Giannini E, et al. Development of a provisional core set of response measures for clinical trials of systemic sclerosis. Ann Rheum Dis. 2008;67(5):703–9.

    Article  PubMed  CAS  Google Scholar 

  12. Bryan C, Howard Y, Brennan P, et al. Survival following the onset of scleroderma: results from a retrospective inception cohort study of the UK patient population. Br J Rheumatol. 1996;35(11):1122–6.

    Article  PubMed  CAS  Google Scholar 

  13. Ferri C, Valentini G, Cozzi F, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore). 2002;81(2):139–53.

    Article  Google Scholar 

  14. Scussel-Lonzetti L, Joyal F, Raynauld JP, et al. Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002;81(2):154–67.

    Article  Google Scholar 

  15. Valentini G, Della Rossa A, Bombardieri S, et al. European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes. Ann Rheum Dis. 2001;60(6):592–8.

    Article  PubMed  CAS  Google Scholar 

  16. Denton CP, Engelhart M, Tvede N, et al. An open-label pilot study of infliximab therapy in diffuse cutaneous systemic sclerosis. Ann Rheum Dis. 2009;68(9):1433–9.

    Article  PubMed  CAS  Google Scholar 

  17. Denton CP, Merkel PA, Furst DE, et al. Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192. Arthritis Rheum. 2007;56(1):323–33.

    Article  PubMed  CAS  Google Scholar 

  18. Becvar R, Stork J, Pesakova V, et al. Clinical correlations of potential activity markers in systemic sclerosis. Ann N Y Acad Sci. 2005;1051:404–12.

    Article  PubMed  CAS  Google Scholar 

  19. Black CM, McWhirter A, Harrison NK, et al. Serum type III procollagen peptide concentrations in systemic sclerosis and Raynaud’s ­phenomenon: relationship to disease activity and duration. Br J Rheumatol. 1989;28(2):98–103.

    Article  PubMed  CAS  Google Scholar 

  20. Nagy Z, Czirjak L. Increased levels of amino terminal propeptide of type III procollagen are an unfavourable predictor of survival in systemic sclerosis. Clin Exp Rheumatol. 2005;23(2):165–72.

    PubMed  CAS  Google Scholar 

  21. Prockop DJ, Kivirikko KI, Tuderman L, et al. The biosynthesis of collagen and its disorders (first of two parts). N Engl J Med. 1979;301(1):13–23.

    Article  PubMed  CAS  Google Scholar 

  22. Dziadzio M, Smith RE, Abraham DJ, et al. Serological assessment of type I collagen burden in scleroderma spectrum disorders: a systematic review. Clin Exp Rheumatol. 2004;22(3):356–67.

    PubMed  CAS  Google Scholar 

  23. McHugh NJ, Distler O, Giacomelli R, et al. Non organ based laboratory markers in systemic sclerosis. Clin Exp Rheumatol. 2003;21(3 Suppl 29):S32–8.

    PubMed  CAS  Google Scholar 

  24. Dziadzio M, Smith RE, Abraham DJ, et al. Circulating levels of active transforming growth factor beta1 are reduced in diffuse cutaneous systemic sclerosis and correlate inversely with the modified Rodnan skin score. Rheumatology (Oxford). 2005;44(12):1518–24.

    Article  CAS  Google Scholar 

  25. Antiga E, Quaglino P, Bellandi S, et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br J Dermatol. 2010;162(5):1056–63.

    Article  PubMed  CAS  Google Scholar 

  26. Sato S, Nagaoka T, Hasegawa M, et al. Elevated serum KL-6 levels in patients with systemic sclerosis: association with the severity of ­pulmonary fibrosis. Dermatology. 2000;200(3):196–201.

    Article  PubMed  CAS  Google Scholar 

  27. Vesely R, Vargova V, Ravelli A, et al. Serum level of KL-6 as a marker of interstitial lung disease in patients with juvenile systemic sclerosis. J Rheumatol. 2004;31(4):795–800.

    PubMed  Google Scholar 

  28. Yamane K, Ihn H, Kubo M, et al. Serum levels of KL-6 as a useful marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. J Rheumatol. 2000;27(4):930–4.

    PubMed  CAS  Google Scholar 

  29. Yanaba K, Hasegawa M, Hamaguchi Y, et al. Longitudinal analysis of serum KL-6 levels in patients with systemic sclerosis: association with the activity of pulmonary fibrosis. Clin Exp Rheumatol. 2003;21(4):429–36.

    PubMed  CAS  Google Scholar 

  30. Kumanovics G, Minier T, Radics J, et al. Comprehensive investigation of novel serum markers of pulmonary fibrosis associated with systemic sclerosis and dermato/polymyositis. Clin Exp Rheumatol. 2008;26(3):414–20.

    PubMed  CAS  Google Scholar 

  31. Asano Y, Ihn H, Yamane K, et al. Clinical significance of surfactant protein D as a serum marker for evaluating pulmonary fibrosis in patients with systemic sclerosis. Arthritis Rheum. 2001;44(6):1363–9.

    Article  PubMed  CAS  Google Scholar 

  32. Hant FN, Ludwicka-Bradley A, Wang HJ, et al. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol. 2009;36(4):773–80.

    Article  PubMed  CAS  Google Scholar 

  33. Woessner Jr JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Arch Biochem Biophys. 1961;93:440–7.

    Article  PubMed  CAS  Google Scholar 

  34. Farina G, Lafyatis D, Lemaire R, et al. A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 2010;62(2):580–8.

    Article  PubMed  CAS  Google Scholar 

  35. Colburn WA. Optimizing the use of biomarkers, surrogate endpoints, and clinical endpoints for more efficient drug development. J Clin Pharmacol. 2000;40(12 Pt 2):1419–27.

    PubMed  CAS  Google Scholar 

  36. Beyer C, Distler JH, Allanore Y, et al. EUSTAR biobanking: recommendations for the collection, storage and distribution of biospecimens in scleroderma research. Ann Rheum Dis. 2011;70:1178–82.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine 3 and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Erlangen, Germany

    Christian Beyer MD

  2. Department of Rheumatology, Center of Experimental Rheumatology and Center of Integrative Human Physiology, University Hospital of Zurich, Zurich, Switzerland

    Oliver Distler MD

  3. Department of Internal Medicine 3, University of Erlangen-Nuremberg, Erlangen, Germany

    Jörg H. W. Distler MD

Authors
  1. Christian Beyer MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oliver Distler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jörg H. W. Distler MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oliver Distler MD .

Editor information

Editors and Affiliations

  1. Feinberg School of Medicine, Northwestern University, E. Huron Street 240, Chicago, 60611-2909, Illinois, USA

    John Varga

  2. Royal Free and University College, Medical School, University College London, Rowland Street, London, NW3 2PF, United Kingdom

    Christopher P. Denton

  3. School of Medicine, Div. Rheumatology, Johns Hopkins University, Eastern Avenue 5200, Baltimore, 21224, Maryland, USA

    Fredrick M. Wigley

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Beyer, C., Distler, O., Distler, J.H.W. (2012). Biomarkers of Fibrosis. In: Varga, J., Denton, C., Wigley, F. (eds) Scleroderma. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-5774-0_23

Download citation

  • DOI: https://doi.org/10.1007/978-1-4419-5774-0_23

  • Published:

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-5773-3

  • Online ISBN: 978-1-4419-5774-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation