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Rheumatology International

Erschienen in:

01.11.2012 | Original Article

Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study

verfasst von: Anne C. Bay-Jensen, Diana J. Leeming, Arndt Kleyer, Sanne S. Veidal, Georg Schett, Morten A. Karsdal

Erschienen in: Rheumatology International | Ausgabe 11/2012

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Abstract

Ankylosing spondylitis (AS) is characterized by gradual cementation of the vertebrae, a process that is described by excessive extracellular matrix remodeling. Specific matrix metalloproteinase (MMP)-derived collagen fragments are released to the circulation, and measurement of those might act as biomarkers of ankylosis. The aim of the study was to investigate the diagnostic value of five novel assays measuring different collagen species. Five newly developed ELISAs measuring MMP-degraded collagen fragments in serum of 40 AS patients and 40 age-matched controls were measured: collagen type I (C1M), type II (C2M), type III (C3M), type IV (C4M) and type VI (C6M) as well as the bone formation marker osteocalcin. The levels of the five collagen neoepitopes were significantly higher in AS patients, except for osteocalcin. Cartilage degradation (C2M) was only significantly correlated with the basement membrane (C4M) in the AS patients. In contrast, C3M was significantly correlated with all of the other collagen markers. The highest diagnostic value was achieved when combining the C2M, C3M and C6M markers, AUC 87% (P < 0.0001). Moreover, a combination of the markers correlated with the clinical mSASS score (P = 0.004, R = 0.44). Novel and unique biomarkers of tissue remodeling may provide diagnostic value and aid in understanding of the AS pathology. Each of the biomarkers tells a unique story, and by combining them in a panel there, we found a strong correlation with mSASSS. We speculate that such panel will be a valuable tool for monitoring patients as effect of treatment, for the prediction of responders and for diagnostic purposes.

Karsdal MA, Henriksen K, Leeming DJ, Mitchell P, Duffin K, Barascuk N et al (2009) Biochemical markers and the FDA critical path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development. Biomarkers 14(3):181–202PubMedCrossRef

Sondergaard BC, Henriksen K, Wulf H, Oestergaard S, Schurigt U, Brauer R et al (2006) Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation. Osteoarthr Cartil 14(8):738–748PubMedCrossRef

Tam LS, Gu J, Yu D (2010) Pathogenesis of ankylosing spondylitis. Nat Rev Rheumatol 6(7):399–405PubMedCrossRef

Braun J, Pincus T (2002) Mortality, course of disease and prognosis of patients with ankylosing spondylitis. Clin Exp Rheumatol 20(6 Suppl 28):S16–S22PubMed

Dakwar E, Reddy J, Vale FL, Uribe JS (2008) A review of the pathogenesis of ankylosing spondylitis. Neurosurg Focus 24(1):E2PubMedCrossRef

Kumar V, Abbas AK, Fausto N, Aster JC (2010) Tissue renewal, regeneration and repair. In: Robbins, Cotran (eds) Pathologic basis of disease, 8th edn. Elsevier, Philadelphia, pp 79–110

Schuppan D, Ruehl M, Somasundaram R, Hahn EG (2001) Matrix as a modulator of hepatic fibrogenesis. Semin Liver Dis 21(3):351–372PubMedCrossRef

Lochter A, Bissell MJ (1999) An odyssey from breast to bone: multi-step control of mammary metastases and osteolysis by matrix metalloproteinases. APMIS 107:128–136PubMedCrossRef

Karsdal MA, Madsen SH, Christiansen C, Henriksen K, Fosang AJ, Sondergaard BC (2008) Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity. Arthritis Res Ther 10(3):R63PubMedCrossRef

10.

Bay-Jensen AC, Hoegh-Madsen S, Dam E, Henriksen K, Sondergaard BC, Pastoureau P et al (2010) Which elements are involved in reversible and irreversible cartilage degradation in osteoarthritis? Rheumatol Int 30(4):435–442

11.

Zhen EY, Brittain IJ, Laska DA, Mitchell PG, Sumer EU, Karsdal MA et al (2008) Characterization of metalloprotease cleavage products of human articular cartilage. Arthritis Rheum 58(8):2420–2431PubMedCrossRef

12.

Schaller S, Henriksen K, Hoegh-Andersen P, Sondergaard BC, Sumer EU, Tanko LB et al (2005) In vitro, ex vivo, and in vivo methodological approaches for studying therapeutic targets of osteoporosis and degenerative joint diseases: how biomarkers can assist? Assay Drug Dev Technol 3:553–580PubMedCrossRef

13.

Leeming DJ, He Y, Veidal S, Nguyen Q, Larsen D, Koizumi M, Segovia-Silvestre T, Zhang C, Zheng Q, Sun S, Cao Y, Barkholt V, Hägglund P, Bay-Jensen A, Qvist P, Karsdal M (2011) A novel marker for assessment of liver matrix remodeling: an enzyme-linked immunosorbent assay (ELISA) detecting a MMP generated type I collagen neo-epitope (C1M). Biomarkers 16(7):616–628

14.

Bay-Jensen AC, Liu Q, Byrjalsen I, Li Y, Wang J, Pedersen C et al (2011) Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, C. Clin Biochem (Epub ahead of print)

15.

Barascuk N, Veidal SS, Larsen L, Larsen DV, Larsen MR, Wang J et al (2010) A novel assay for extracellular matrix remodeling associated with liver fibrosis: an enzyme-linked immunosorbent assay (ELISA) for a MMP-9 proteolytically revealed neo-epitope of type III collagen. Clin Biochem (in press)

16.

Rosenquist C, Bonde M, Fledelius C, Qvist P (1994) A simple enzyme-linked immunosorbent assay of human osteocalcin. Clin Chem 40(7):1258–1264PubMed

17.

Muntean L, Rojas-Vargas M, Font P, Simon SP, Rednic S, Schiotis R et al (2011) Relative value of the lumbar spine and hip bone mineral density and bone turnover markers in men with ankylosing spondylitis. Clin Rheumatol

18.

Maksymowych WP, Morency N, Wichuk S, Rahman P, Gladman DD, Inman Rd (2010) Multiplex assay of a panel of 58 biomarkers in ankylosing spondylitis: identification of high priority candidates for prediction of structural damage. Ann Rheum Dis 69(Suppl. 3):428

19.

20.

Leeming DJ, Larsen DV, Zhang C, Hi Y, Veidal SS, Nielsen RH et al (2010) Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)–assessment of corresponding epitopes. Clin Biochem 43(15):1249–1256PubMedCrossRef

21.

Bay-Jensen AC, liu Q, Byrjalsen I, li Y, Wang J, Pedersen C et al (2010) Serum CIIM level in subjects with severe radiographic osteoarthritis; Description of a new metalloproteinase-derived cartilage biomarker. PONE 1 September 2010 (Submitted)

22.

Schett G (2007) Erosive arthritis. Arthritis Res Ther 9(Suppl 1):S2PubMedCrossRef

23.

Schett G (2009) Bone formation versus bone resorption in ankylosing spondylitis. Adv Exp Med Biol 649:114–121PubMedCrossRef

24.

Schett G, Teitelbaum SL (2009) Osteoclasts and Arthritis. J Bone Miner Res 24(7):1142–1146CrossRef

25.

Schett G (2009) Osteoimmunology in rheumatic diseases. Arthritis Res Ther 11(1):210PubMedCrossRef

26.

Ruof J, Stucki G (1999) Validity aspects of erythrocyte sedimentation rate and C-reactive protein in ankylosing spondylitis: a literature review. J Rheumatol 26(4):966–970PubMed

27.

Spoorenberg A, van der Heijde D, de Klerk E, Dougados M, de Vlam K, Mielants H et al (1999) Relative value of erythrocyte sedimentation rate and C-reactive protein in assessment of disease activity in ankylosing spondylitis. J Rheumatol 26(4):980–984PubMed

28.

Maksymowych WP, Dhillon SS, Park R, Salonen D, Inman RD, Lambert RG (2007) Validation of the spondyloarthritis research consortium of Canada magnetic resonance imaging spinal inflammation index: is it necessary to score the entire spine? Arthritis Rheum 57(3):501–507PubMedCrossRef

29.

Wanders AJ, Landewe RB, Spoorenberg A, Dougados M, van der Linden LS, Mielants H et al (2004) What is the most appropriate radiologic scoring method for ankylosing spondylitis? A comparison of the available methods based on the Outcome Measures in Rheumatology Clinical Trials filter. Arthritis Rheum 50(8):2622–2632PubMedCrossRef

30.

de Vries MK, van Eijk I, van der Horst-Bruinsma IE, Peters MJ, Nurmohamed MT, Dijkmans BA et al (2009) Erythrocyte sedimentation rate, C-reactive protein level, and serum amyloid a protein for patient selection and monitoring of anti-tumor necrosis factor treatment in ankylosing spondylitis. Arthritis Rheum 61(11):1484–1490PubMedCrossRef

31.

Gelse K, Poschl E, Aigner T (2003) Collagens–structure, function, and biosynthesis. Adv Drug Deliv Rev 55(12):1531–1546PubMedCrossRef

32.

33.

Hudson BG, Reeders ST, Tryggvason K (1993) Type IV collagen: structure, gene organization, and role in human diseases. Molecular basis of Goodpasture and Alport syndromes and diffuse leiomyomatosis. J Biol Chem 268(35):26033–26036PubMed

34.

Kielty CM, Whittaker SP, Grant ME, Shuttleworth CA (1992) Type VI collagen microfibrils: evidence for a structural association with hyaluronan. J Cell Biol 118(4):979–990PubMedCrossRef

35.

Franck H, Meurer T, Hofbauer LC (2004) Evaluation of bone mineral density, hormones, biochemical markers of bone metabolism, and osteoprotegerin serum levels in patients with ankylosing spondylitis. J Rheumatol 31(11):2236–2241PubMed

36.

37.

Appel H, Ruiz-Heiland G, Listing J, Zwerina J, Herrmann M, Mueller R et al (2009) Altered skeletal expression of sclerostin and its link to radiographic progression in ankylosing spondylitis. Arthritis Rheum 60(11):3257–3262PubMedCrossRef

38.

Schett G, Rudwaleit M (2010) Can we stop progression of ankylosing spondylitis? Best Pract Res Clin Rheumatol 24(3):363–371PubMedCrossRef

39.

40.

41.

42.

Veidal SS, Karsdal MA, Nawrocki A, Larsen MR, Dai Y, Zheng Q, Hägglund P, Vainer B, Skjøt-Arkil H, Leeming DJ (2011) Assessment of proteolytic degradation of the basement membrane: a fragment of type IV collagen as a biochemical marker for liver fibrosis. Fibrogenesis Tissue Repair 4:22

43.

Veidal SS, Karsdal MA, Vassiliadis E, Nawrocki A, Larsen MR, Nguyen QH, Hägglund P, Luo Y, Zheng Q, Vainer B, Leeming DJ (2011) MMP mediated degradation of type VI collagen is highly associated with liver fibrosis—identification and validation of a novel biochemical marker assay. PLoS One 6(9):e24753

Titel: Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study
verfasst von: Anne C. Bay-Jensen
Diana J. Leeming
Arndt Kleyer
Sanne S. Veidal
Georg Schett
Morten A. Karsdal
Publikationsdatum: 01.11.2012
Verlag: Springer-Verlag
Erschienen in: Rheumatology International / Ausgabe 11/2012
Print ISSN: 0172-8172
Elektronische ISSN: 1437-160X
DOI: https://doi.org/10.1007/s00296-011-2237-8

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