title: Arthritogenic anti-type II collagen antibodies are pathogenic for cartilage-derived chondrocytes independent of inflammatory cells.
abstract: OBJECTIVE
  Some monoclonal antibodies (mAb) to type II collagen (CII) are arthritogenic upon passive transfer to mice. We undertook this study to investigate whether such mAb are pathogenic in the absence of mediators of inflammation.
  
  
  METHODS
  The arthritogenic mAb CIIC1 and M2139, and the nonarthritogenic mAb CIIF4, each reactive with a distinct and well-defined conformational epitope on CII, were compared with control mAb GAD6. Bovine chondrocytes were cultured with one of the mAb, and on days 3, 6, and 9, antibody binding by chondrocytes and newly synthesized extracellular matrix (ECM) was examined by immunofluorescence, morphologic effects were studied by electron microscopy, and synthesis of matrix components was determined by metabolic labeling with (3)H-proline for collagen and (35)S-sulfate for proteoglycans.
  
  
  RESULTS
  All 3 mAb to CII bound to the matrix. CIIC1 and M2139 adversely affected the cultures, whereas CIIF4 did not. CIIC1 caused disorganization of CII fibrils in the ECM without affecting chondrocyte morphology, and increased matrix synthesis. M2139 caused thickening and aggregation of CII fibrils in the ECM and abnormal chondrocyte morphology but matrix synthesis was unaffected.
  
  
  CONCLUSIONS
  The unique arthritogenic capacity of particular anti-CII mAb upon passive transfer could be explained by their adverse, albeit differing, effects in primary cultures of chondrocytes. Such effects occur independent of inflammation mediators and are related to the epitope specificity of the mAb. Interference with the structural integrity of CII could precede, and even initiate, the inflammatory expression of disease.
authors.affiliation: Monash University, Clayton, Victoria, Australia.
authors.forename: S Fatemah
authors.initials: SF
authors.lastname: Amirahmadi
authors.forename: Senga
authors.initials: S
authors.lastname: Whittingham
authors.forename: Duncan E
authors.initials: DE
authors.lastname: Crombie
authors.forename: Kutty Selva
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
authors.forename: Ian R
authors.initials: IR
authors.lastname: Mackay
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: van Damme
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Rowley
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001168:Arthritis / Q000276:immunology*; D015415:Biomarkers; D002356:Cartilage / Q000276:immunology; D019902:Chondrocytes / Q000276:immunology*; D024043:Collagen Type II / Q000276:immunology*; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D024043:Collagen Type II