Myers L K, Rosloniec E F, Cremer M A, Kang A H
Department of Medicine, University of Tennessee, Memphis 38163, USA.
Life Sci. 1997;61(19):1861-78. doi: 10.1016/s0024-3205(97)00480-3.
Collagen induced arthritis (CIA) is an autoimmune model that in many ways resembles rheumatoid arthritis (RA). Immunization of genetically susceptible strains of rodents and primates with type II collagen (CII) leads to the development of a severe polyarticular arthritis that is mediated by an autoimmune response. Like RA, synovitis and erosions of cartilage and bone are hallmarks of CIA, and susceptibility to both RA and CIA is linked to the expression of specific MHC class II molecules. Although not identical to RA, CIA clearly establishes the biological plausibility that an autoimmune reaction to a cartilage component can lead to a chronic, destructive, polyarthritis. Although it is induced in susceptible animals by immunization with heterologous CII, it is the autoreactive component of the immune response that leads to disease. A wealth of evidence indicates that synovitis is initiated by the production of pathogenic autoreactive antibodies capable of fixing and activating complement. The elucidation of the specific amino acid sequences of collagen that are recognized by the MHC molecules has enabled at least two approaches to specific immunotherapy to be considered. Firstly, small synthetic peptides representing dominant epitopes have been used as effectively as the original antigen as a tolerogen. The rather fastidious physicochemical properties of collagen that make it difficult for its routine use in therapy are thereby circumvented by the use of oligopeptides. Secondly, analysis of the specific amino acid side chains that are involved in MHC contact and TCR recognition enables analog peptides to be devised which can specifically and exquisitely inhibit the response to CII, preventing the onset of arthritis. Further investigations involving this model may contribute to the development of specific immunotherapies in the human disorder.
胶原诱导性关节炎（CIA）是一种自身免疫模型，在许多方面类似于类风湿关节炎（RA）。用II型胶原（CII）对啮齿动物和灵长类动物的遗传易感品系进行免疫会导致严重的多关节关节炎的发展，这种关节炎由自身免疫反应介导。与RA一样，滑膜炎以及软骨和骨侵蚀是CIA的标志，对RA和CIA的易感性都与特定MHC II类分子的表达有关。尽管CIA与RA并不完全相同，但它明确证实了对软骨成分的自身免疫反应可导致慢性、破坏性多关节炎的生物学合理性。尽管它是通过用异源CII免疫易感动物诱导产生的，但导致疾病的是免疫反应中的自身反应性成分。大量证据表明，滑膜炎是由能够固定和激活补体的致病性自身反应性抗体的产生引发的。对MHC分子识别的胶原特定氨基酸序列的阐明使得至少两种特异性免疫疗法的方法得以考虑。首先，代表显性表位的小合成肽已被用作耐受原，其效果与原始抗原一样有效。胶原相当挑剔的物理化学性质使其难以常规用于治疗，而使用寡肽则可规避这一问题。其次，对参与MHC接触和TCR识别的特定氨基酸侧链的分析使得能够设计出模拟肽，这些模拟肽可以特异性且精确地抑制对CII的反应，从而预防关节炎的发作。涉及该模型的进一步研究可能有助于人类疾病中特异性免疫疗法的开发。
