title: Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis.
abstract: OBJECTIVE
  Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage, where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint disease, such as rheumatoid arthritis (RA) and osteoarthritis (OA). This study was undertaken to investigate the ability of COMP to regulate complement, a capacity that has previously been shown for some other cartilage proteins.
  
  
  METHODS
  Regulation of complement by COMP was studied using functional in vitro assays. Inter-actions between complement proteins and COMP were investigated by direct binding assay and electron microscopy. Circulating COMP and COMP-C3b complexes in serum and synovial fluid from RA and OA patients and healthy controls were measured with a novel enzyme-linked immunosorbent assay.
  
  
  RESULTS
  We found in vivo evidence of complement activation by released COMP in the general circulation of patients with RA, but not patients with OA. COMP induced activation and deposition of C3b and C9 specifically via the alternative pathway of complement, which was attributable to direct interaction between COMP and properdin. Furthermore, COMP inhibited the classical and the lectin complement pathways due to direct interaction with the stalk region of C1q and mannose-binding lectin, respectively.
  
  
  CONCLUSIONS
  COMP is the first extracellular matrix protein for which an active role in inflammation has been demonstrated in vivo. It can activate one complement pathway at the same time as it has the potential to inhibit another. The net outcome of these interactions is most likely determined by the type of released COMP fragments, which may be disease specific.
authors.affiliation: Lund University, Malmö, Sweden.
authors.forename: Kaisa E
authors.initials: KE
authors.lastname: Happonen
authors.forename: Tore
authors.initials: T
authors.lastname: Saxne
authors.forename: Anders
authors.initials: A
authors.lastname: Aspberg
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.forename: Dick
authors.initials: D
authors.lastname: Heinegård
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D064236:Cartilage Oligomeric Matrix Protein; D016022:Case-Control Studies; D015922:Complement C1q / Q000378:metabolism; D003179:Complement C3b / Q000378:metabolism; D003186:Complement C9 / Q000378:metabolism; D003165:Complement System Proteins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D037601:Mannose-Binding Lectin / Q000378:metabolism; D064235:Matrilin Proteins; D008875:Middle Aged; D010003:Osteoarthritis / Q000175:diagnosis* / Q000378:metabolism*; D011414:Properdin / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D015415:Biomarkers; D064236:Cartilage Oligomeric Matrix Protein; D003186:Complement C9; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D037601:Mannose-Binding Lectin; D064235:Matrilin Proteins; C577553:TSP5 protein, human; D011414:Properdin; D015922:Complement C1q; D003179:Complement C3b; D003165:Complement System Proteins