Arthritogenic anti–type II collagen antibodies are pathogenic for cartilage-derived chondrocytes independent of inflammatory cells
Article first published online: 2 JUN 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 6, pages 1897–1906, June 2005
How to Cite
Amirahmadi, S. F., Whittingham, S., Crombie, D. E., Nandakumar, K. S., Holmdahl, R., Mackay, I. R., van Damme, M.-P. and Rowley, M. J. (2005), Arthritogenic anti–type II collagen antibodies are pathogenic for cartilage-derived chondrocytes independent of inflammatory cells. Arthritis & Rheumatism, 52: 1897–1906. doi: 10.1002/art.21097
- Issue published online: 2 JUN 2005
- Article first published online: 2 JUN 2005
- Manuscript Accepted: 9 MAR 2005
- Manuscript Received: 17 SEP 2004
- National Health and Medical Research Council of Australia
- Arthritis Foundation of Australia
- Swedish Science Research Council
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.
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 3H-proline for collagen and 35S-sulfate for proteoglycans.
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.
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.