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

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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.

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Abbreviations

AS:

Ankylosing spondylitis

AUC:

Area under the curve

CO:

Collagen

CRP:

C-reactive protein

ECM:

Extracellular matrix

ESR:

Erythrocyte sedimentation rate

MMP:

Metalloproteinase

OA:

Osteoarthritis

RA:

Rheumatoid arthritis

SpA:

Spondyloarthropathy

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Acknowledgments

We would like to thank the technicians Maibritt Andersen, Sedi Tavaelee, Lise Larsen, Quoc Hai Trieu Nguyen and Dorthe Vang Larsen of the Nordic Bioscience assay development laboratory, for assisting the development of the novel biomarkers assays presented in the manuscript. The work of Georg Schett was supported by the Deutsche Forschungsgemeinschaft (SPP1468-IMMUNOBONE), the Bundesministerium für Bildung und Forschung (BMBF; ANCYLOSS) and the MASTERSWITCH and IMI projects of the European Union. The work presented in this article has been conducted with unrestricted support from the Danish research fund (Den danske forsknings fond).

Conflict of interest

All, but Arndt Kleyer and George Schett, were employed by Nordic Bioscience while this study was conducted. The biochemical markers presented in the article are for research use only. Morten Karsdal holds stock in Nordic Bioscience. Other authors have no competing interests.

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Correspondence to Anne C. Bay-Jensen.

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Bay-Jensen, A.C., Leeming, D.J., Kleyer, A. et al. Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study. Rheumatol Int 32, 3565–3572 (2012). https://doi.org/10.1007/s00296-011-2237-8

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