title: Enzyme-linked immunosorbent assay (ELISAs) for metalloproteinase derived type II collagen neoepitope, CIIM--increased serum CIIM in subjects with severe radiographic osteoarthritis.
abstract: OBJECTIVE
  In joint degenerative diseases, the collagens are degraded by matrix metalloproteinases and protein fragments are released to serum as potential biomarkers.
  
  
  METHODS
  A collagen type II specific neoepitope, CIIM, was identified (…RDGAAG(1053)) by mass spectrometry. Two ELISAs against the neoepitope were developed. CIIM was measured in cartilage explants in the presence or absence of protease inhibitors. CIIM was measured in OA synovial fluid (n=51) and serum (n=156). Knee OA was graded by standard Kellgren-Lawrence (KL) score.
  
  
  RESULTS
  The ELISAs showed good technical performance; CV%, <13%. CIIM release from cartilage explants was blocked by the MMP inhibitor. CIIM was detected in synovial fluid. Furthermore, serum CIIM levels were significantly higher (P<0.05) in those individuals with mild or severe OA than in those with no OA.
  
  
  CONCLUSIONS
  We developed a new biomarker for joint degenerative diseases, which we demonstrated was derived from MMP-degraded type II collagen.
authors.affiliation: Cartilage Biology and Biomarkers R&D, Nordic Bioscience, Herlev, Denmark.
authors.forename: Anne-Christine
authors.initials: AC
authors.lastname: Bay-Jensen
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.forename: Inger
authors.initials: I
authors.lastname: Byrjalsen
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Jianxia
authors.initials: J
authors.lastname: Wang
authors.forename: Christian
authors.initials: C
authors.lastname: Pedersen
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Leeming
authors.forename: Erik B
authors.initials: EB
authors.lastname: Dam
authors.forename: Qinlong
authors.initials: Q
authors.lastname: Zheng
authors.forename: Per
authors.initials: P
authors.lastname: Qvist
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D024043:Collagen Type II / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D045726:Metalloproteases / Q000097:blood*; D008875:Middle Aged; D010003:Osteoarthritis / Q000097:blood* / Q000201:enzymology
chemical_list: D024043:Collagen Type II; D045726:Metalloproteases