- Meeting abstract
- Open Access
Collagen Type II-Specific Autoantibodies in Chronic Inflammatory Joint Diseases
Arthritis Research & Therapyvolume 1, Article number: S27 (1999)
Cartilage components are considered a source of antigens that could continously fuel tissue-specific immune reactions directed to the joints. One of the structural components is collagen type II (CII), the predominant collagen type in cartilage. Immunization with CII is associated with the development of an experimental autoimmune arthritis in mice and rats [1,2]. Collagen-induced arthritis (CIA) is a relevant experimental model for rheumatoid arthritis (RA) . The induction of CIA is critically dependent on immunization with CII in its native conformation, and the onset of arthritis is preceded by an early rise in IgG autoantibodies (Abs) that are specific for triple helical structures on CII . The preparation of a large panel of recombinant chimeric collagen molecules enabled us to determine precisely the epitopes on CII that are recognized by monoclonal antibodies established from arthritis prone DBA/1 mice . The insertion of a series of CII cassettes into the triple helical recombinant collagen X allowed the identification of 5 triple helical immunodominant domains of 5-11 amino acid length, to which the majority of the mAbs bound . In addition, a separate epitope has been identified that seems to be a major target of the B-cell response in the rat model of CIA. Interestingly, some of the epitopes that have been characterized in the rodent arthritis models are also target structures of the CII-specific IgG response in patients suffering from severe RA. The results indicate that the arthritogenic B-cell response is directed to evolutionary conserved CII-structures.
Supported by a grant from the Deutsche Forschungsgemeinschaft: SFB 263, project C3 and the European Commission (Bio4-98-0479).
Courtenay JS, Dallman MJ, Dayan AD, Martin A, Mosedale B: Immunisation against heterologous type II collagen induces arthritis in mice. Nature. 1980, 283: 666-668. 10.1038/283666a0.
Trentham DE, Townes AS, Kang AH: Autoimmunity to type II collagen an experimental model of arthritis. J Exp Med. 1977, 146: 857-868. 10.1084/jem.146.3.857.
Holmdahl R, Andersson M, Goldschmidt TJ, Gustafsson K, Jansson L, Mo JA: Type II collagen autoimmunity in animals and provocations leading to arthritis. Immunol Rev. 1990, 118: 193-232.
Holmdahl R, Rubin K, Klareskog L, Larsson E, Wigzell H: Characterization of the antibody response in mice with type II collagen-induced arthritis, using monoclonal anti-type II collagen antibodies. Arthritis Rheum. 1986, 29: 400-410.
Schulte S, Unger C, Mo JA, et al: Arthritis-related B cell epitopes in collagen II are conformation-dependent and sterically privileged in accessible sites of cartilage collagen fibrils. J Biol Chem. 1998, 273: 1551-1561. 10.1074/jbc.273.3.1551.