The FASEB Journal, Vol 2, 2950-2956, Copyright © 1988 by The Federation of American Societies for Experimental Biology

REVIEWS

Collagen autoimmunity and arthritis

JM Stuart, WC Watson and AH Kang
Department of Medicine, University of Tennessee, Memphis.

Collagen-induced arthritis in animals is an example of polyarthritis that sufficiently resembles human rheumatoid arthritis to be used as a model. It is caused by immunizing susceptible animals with type II collagen isolated from articular cartilage. Susceptibility is genetically determined and linked to the major histocompatibility locus. It is important because some human arthritis is also associated with major histocompatibility genes and may be caused or aggravated by the presence of autoimmunity to normal cartilage components. Collagen- induced arthritis is also important because it is an example of immunologically mediated joint destruction, which may share some of the mechanisms present in human disease. Although it is caused by autoimmunity to collagen, susceptibility and responsiveness to type II collagen are not completely correlated, and there are examples of animals with high levels of collagen immunity who do not develop arthritis. The initial lesion appears to be the deposition of an antibody on the surface of articular cartilage, which precedes development of overt arthritis by several days. Disease can be readily transferred with specific antibody. Arthritogenic antibodies appear to have restricted epitope specificity, which may partially explain the disparities between responsiveness to immunization with collagen and susceptibility to arthritis, but precise delineation of the epitopes involved has not yet been accomplished. Complement activation also appears to be intimately involved since the disease correlates with the presence of high levels of complement-binding IgG isotypes, and passive transfer is possible only into complement-sufficient recipients. Inflammation progresses rapidly so that cartilage destruction and marginal erosion develop over a period of a few days. Collagen-induced arthritis offers a unique opportunity to study autoimmune-mediated arthritis in which the inducing antigen is well characterized and readily available. Analysis of the disease has permitted the proposal of a schema for its pathogenesis.

This article has been cited by other articles:

				Y. Yamanishi, D. L. Boyle, M. J. Pinkoski, A. Mahboubi, T. Lin, Z. Han, N. J. Zvaifler, D. R. Green, and G. S. Firestein Regulation of Joint Destruction and Inflammation by p53 in Collagen-Induced Arthritis Am. J. Pathol., January 1, 2002; 160(1): 123 - 130. [Abstract] [Full Text] [PDF]

				C. J. Krco, S. Watanabe, J. Harders, M. M. Griffths, H. Luthra, and C. S. David Identification of T Cell Determinants on Human Type II Collagen Recognized by HLA-DQ8 and HLA-DQ6 Transgenic Mice J. Immunol., August 1, 1999; 163(3): 1661 - 1665. [Abstract] [Full Text] [PDF]

				T. M. Haqqi, D. D. Anthony, S. Gupta, N. Ahmad, M.-S. Lee, G. K. Kumar, and H. Mukhtar Prevention of collagen-induced arthritis in mice by a polyphenolic fraction from green tea PNAS, April 13, 1999; 96(8): 4524 - 4529. [Abstract] [Full Text] [PDF]

				Y. Zhang, A. Guerassimov, J.-Y. Leroux, A. Cartman, C. Webber, R. Lalic, E. de Miguel, L. C. Rosenberg, and A. R. Poole Induction of Arthritis in BALB/c Mice by Cartilage Link Protein : Involvement of Distinct Regions Recognized by T and B Lymphocytes Am. J. Pathol., October 1, 1998; 153(4): 1283 - 1291. [Abstract] [Full Text] [PDF]