title: Ankylosing spondylitis is characterized by an increased turnover of several different metalloproteinase-derived collagen species: a cross-sectional study.
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.
authors.affiliation: Cartilage Biology and Biomarkers, R&D, Nordic Bioscience, Hovedgade 207, 2730 Herlev, Denmark. acbj@nordicbioscience.com
authors.forename: Anne C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Arndt
authors.initials: A
authors.lastname: Kleyer
authors.forename: Sanne S
authors.initials: SS
authors.lastname: Veidal
authors.forename: Georg
authors.initials: G
authors.lastname: Schett
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D003094:Collagen / Q000097:blood*; D003430:Cross-Sectional Studies; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000097:blood*; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000175:diagnosis* / Q000473:pathology
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D015675:Osteocalcin; D003094:Collagen; D045726:Metalloproteases
references.citation: Neurosurg Focus. 2008;24(1):E2
references.pmid: 18290740
references.citation: Semin Liver Dis. 2001 Aug;21(3):351-72
references.pmid: 11586465
references.citation: Arthritis Rheum. 2009 Nov 15;61(11):1484-90
references.pmid: 19877087
references.citation: J Rheumatol. 1999 Apr;26(4):980-4
references.pmid: 10229432
references.citation: Rheumatol Int. 2010 Feb;30(4):435-42
references.pmid: 19816688
references.citation: J Rheumatol. 2004 Nov;31(11):2236-41
references.pmid: 15517638
references.citation: Arthritis Rheum. 2009 Nov;60(11):3257-62
references.pmid: 19877044
references.citation: Best Pract Res Clin Rheumatol. 2010 Jun;24(3):363-71
references.pmid: 20534370
references.citation: Clin Exp Rheumatol. 2002 Nov-Dec;20(6 Suppl 28):S16-22
references.pmid: 12463441
references.citation: Assay Drug Dev Technol. 2005 Oct;3(5):553-80
references.pmid: 16305312
references.citation: Clin Biochem. 2010 Jul;43(10-11):899-904
references.pmid: 20380828
references.citation: J Bone Miner Res. 2009 Jul;24(7):1142-6
references.pmid: 19557892
references.citation: Arthritis Res Ther. 2008;10(3):R63
references.pmid: 18513402
references.citation: J Cell Biol. 1992 Aug;118(4):979-90
references.pmid: 1323568
references.citation: PLoS One. 2011;6(9):e24753
references.pmid: 21935455
references.citation: Arthritis Rheum. 2004 Aug;50(8):2622-32
references.pmid: 15334477
references.citation: Arthritis Rheum. 2007 Apr 15;57(3):501-7
references.pmid: 17394179
references.citation: Adv Drug Deliv Rev. 2003 Nov 28;55(12):1531-46
references.pmid: 14623400
references.citation: APMIS. 1999 Jan;107(1):128-36
references.pmid: 10190289
references.citation: Adv Exp Med Biol. 2009;649:114-21
references.pmid: 19731624
references.citation: Nat Rev Rheumatol. 2010 Jul;6(7):399-405
references.pmid: 20517295
references.citation: Arthritis Res Ther. 2009;11(1):210
references.pmid: 19232069
references.citation: J Biol Chem. 1993 Dec 15;268(35):26033-6
references.pmid: 8253711
references.citation: Clin Chem. 1994 Jul;40(7 Pt 1):1258-64
references.pmid: 8013096
references.citation: Clin Rheumatol. 2011 May;30(5):691-5
references.pmid: 21221691
references.citation: Biomarkers. 2011 Nov;16(7):616-28
references.pmid: 21988680
references.citation: Arthritis Rheum. 2008 Aug;58(8):2420-31
references.pmid: 18668564
references.citation: J Rheumatol. 1999 Apr;26(4):966-70
references.pmid: 10229429
references.citation: Fibrogenesis Tissue Repair. 2011 Oct 05;4:22
references.pmid: 21970406
references.citation: Clin Biochem. 2011 Apr;44(5-6):423-9
references.pmid: 21223960
references.citation: Biomarkers. 2009 May;14(3):181-202
references.pmid: 19399662
references.citation: Clin Biochem. 2010 Oct;43(15):1249-56
references.pmid: 20709044
references.citation: Arthritis Res Ther. 2007;9 Suppl 1:S2
references.pmid: 17634141
references.citation: Osteoarthritis Cartilage. 2006 Aug;14(8):738-48
references.pmid: 16563811