title: Investigation of two novel biochemical markers of inflammation, matrix metalloproteinase and cathepsin generated fragments of C-reactive protein, in patients with ankylosing spondylitis.
abstract: OBJECTIVE
  Ankylosing spondylitis (AS) is a chronic inflammation of the spine and the sacroiliac joints. Current markers of inflammation, such as C-reactive protein (CRP), are reflecting the production of an acute phase reactant rather than tissue specific inflammation, but the use of CRP as a diagnostic and prognostic marker for AS has not provided the sought accuracy and specificity. We hypothesized that local enzymatic activity in the disease-affected tissue, which is associated with extensive tissue turnover may, by cleavage, modify the CRP produced in the liver. These cleavage products may provide additional information on systemic inflammation as compared to that of full-length CRP. We investigated whether these CRP degradation products would provide additional diagnostic value in AS patients compared to full-length CRP.
  
  
  METHODS
  CRP fragments were identified by mass-spectrometry. Two fragments were selected for ELISA development. One assay exclusively identified a matrix metalloproteinase (MMP) generated fragment, CRP-MMP, whereas the other assay identified a cathepsin generated fragment, CRP-CAT. Full-length CRP, CRP-MMP and CRP-CAT were measured in serum samples from 40 AS patients and 40 sex- and age-matched controls.
  
  
  RESULTS
  Full-length CRP was not elevated in AS patients compared to controls, whereas CRP-MMP was elevated by 25% (p<0.001) and CRP-CAT by 50% (p<0.0001). The Area Under Curve of the Receiver-Operator Characteristic curve of CRP-CAT was the highest with 77%.
  
  
  CONCLUSIONS
  MMP and cathepsin degraded CRP provided more discriminative diagnostic potential compared to that of full-length CRP in this current study. These data suggest that different pools of CRP may provide insight into the inflammation processes in AS.
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark. hbe@nordicbioscience.com
authors.forename: H
authors.initials: H
authors.lastname: Skjøt-Arkil
authors.forename: G
authors.initials: G
authors.lastname: Schett
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.forename: D V
authors.initials: DV
authors.lastname: Larsen
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Q
authors.initials: Q
authors.lastname: Zheng
authors.forename: M R
authors.initials: MR
authors.lastname: Larsen
authors.forename: A
authors.initials: A
authors.lastname: Nawrocki
authors.forename: A C
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: K
authors.initials: K
authors.lastname: Henriksen
authors.forename: C
authors.initials: C
authors.lastname: Christiansen
authors.forename: P
authors.initials: P
authors.lastname: Alexandersen
authors.forename: D J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: M A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002403:Cathepsins / Q000097:blood / Q000276:immunology*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000592:standards; D000939:Epitopes / Q000097:blood / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000276:immunology; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D012372:ROC Curve; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000175:diagnosis / Q000276:immunology
chemical_list: D015415:Biomarkers; D000939:Epitopes; D010446:Peptide Fragments; D002097:C-Reactive Protein; D002403:Cathepsins; D020782:Matrix Metalloproteinases