Stuart J M, Watson W C, Kang A H
Department of Medicine, University of Tennessee, Memphis.
FASEB J. 1988 Nov;2(14):2950-6. doi: 10.1096/fasebj.2.14.3053308.
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.
动物中的胶原诱导性关节炎是多关节炎的一个例子，它与人类类风湿性关节炎极为相似，可作为模型使用。它是通过用从关节软骨分离出的II型胶原免疫易感动物而引起的。易感性由基因决定，并与主要组织相容性位点相关。它很重要，因为一些人类关节炎也与主要组织相容性基因有关，并且可能由对正常软骨成分的自身免疫的存在而引发或加重。胶原诱导性关节炎也很重要，因为它是免疫介导的关节破坏的一个例子，这可能与人类疾病中存在的一些机制相同。虽然它是由对胶原的自身免疫引起的，但对II型胶原的易感性和反应性并不完全相关，并且有一些对胶原免疫水平高但未患关节炎的动物实例。最初的病变似乎是抗体在关节软骨表面的沉积，这在明显的关节炎出现前几天就已发生。疾病可以很容易地通过特异性抗体进行转移。致关节炎抗体似乎具有有限的表位特异性，这可能部分解释了对胶原免疫的反应性与对关节炎的易感性之间的差异，但所涉及表位的精确界定尚未完成。补体激活似乎也密切相关，因为该疾病与高水平的补体结合IgG同种型的存在相关，并且只有将其被动转移到补体充足的受体中才有可能。炎症进展迅速，以至于在几天内就会出现软骨破坏和边缘侵蚀。胶原诱导性关节炎为研究自身免疫介导的关节炎提供了一个独特的机会，其中诱导抗原特征明确且易于获得。对该疾病的分析使得能够提出其发病机制的模式。
