Immunogenetics of collagen-induced arthritis in rats.
Immunogenetics of collagen-induced arthritis in rats.
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DOI：
10.3109/08830188809044766
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发表时间：
1988-09-01
影响因子：
5
通讯作者：
Griffiths, M M
中科院分区：
文献类型：
--
作者：
Griffiths, M M
CIA 可以被视为实验诱导的自身免疫的多因素动物模型，该模型针对关节组织并处于多基因控制下。因此，虽然 CIA 的诱导需要对 II 型胶原蛋白的免疫反应，但对 II 型胶原蛋白的高免疫反应并不是 CIA 的特征，表明决定性特异性至关重要。此外，RT1 连锁和非 RT1 连锁的基因定向功能都参与 II 型胶原免疫的最终临床反应。 RT1 相关控制可能在 II 类 (Ia) 分子水平上发挥作用（就像在小鼠中一样），具有对致关节炎与非致关节炎表位的固有选择性，以呈现给免疫反应系统；非 RT1 连锁控制可能反映控制 T 细胞受体、免疫球蛋白亚型或补体成分的基因。还有证据表明，在某些菌株中，潜在病理性抗胶原自身免疫的影响可能会被其他与免疫系统不直接相关的非 RT1 基因控制性状所减弱甚至消除。这些一般性结论与其他研究人员的结论非常一致，他们对小鼠 CIA 的免疫遗传学进行了广泛而深入的研究。 CIA 显然不是任何一种更常见的风湿性疾病的精确模型，例如类风湿性关节炎或系统性红斑狼疮。事实上，它更类似于多软骨炎和其他一些血清阴性结缔组织疾病。然而，在尝试了解影响特定且可定义的自身免疫过程（抗胶原反应性）的遗传和环境因素时，CIA 仍然是一个极其有用的模型。反过来，对胶原蛋白和其他自身抗原的自身免疫是迄今为止已发现的大多数不同人类风湿病综合征的一个促成因素或复杂化方面。本文讨论的大鼠 CIA 模型的特征，即临床疾病的发病率、严重程度、进展速度和表达的遗传控制变异，也是人类风湿病患者群体的特征。同样，多个基因对这些综合征的可能贡献也得到了认可。对中央情报局模型的持续研究预计将产生重要信息，可用于更好地了解其人类模型。
CIA can be viewed as a multifactorial animal model of experimentally-induced autoimmunity that is targeted to joint tissues and under multiple gene control. Thus, although induction of CIA requires immune reactivity to type II collagen, a high immune response to type II collagen is not pathognomonic of CIA, indicating that determinant specificity is of crucial importance. Also, both RT1-linked and non-RT1-linked gene directed functions are involved in the final clinical response to immunization with type II collagen. RT1-linked control is likely exerted at the level of Class II (Ia) molecules (as it is in mice) with inherent selectivity of arthritogenic vs non-arthritogenic epitopes for presentation to the immune response system; non-RT1-linked control may reflect genes controlling T-cell receptors, immunoglobulin subtypes or complement components. There is also evidence that the effects of potentially pathological anti-collagen autoimmunity may in some strains be muted or even obviated by other non-RT1 gene controlled traits that are not directly related to the immune system. These general conclusions are in close accord with those of other investigators who have carefully conducted extensive and in-depth studies of the immunogenetics of CIA in mice. CIA is obviously not an exact model of any one of the more common rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus. In fact, it is more closely analogous to polychondritis and some of the other sero-negative connective tissue diseases. However, CIA remains an extremely useful model in attempts to understand the genetic and environmental factors which influence a specific and definable autoimmune process--anti-collagen reactivity. In turn, autoimmunity to collagen, and to other autoantigens, is a contributing or complicating aspect of most of the diverse human rheumatic disease syndromes which have been identified to date. The characteristics of the CIA model in rats which have been discussed in this article, i.e., genetically controlled variations in incidence, severity, rate of progression and expression of clinical disease, are also characteristic of the human rheumatic disease patient population. Likewise, the probable contribution of multiple genes to these syndromes is recognized. Continued investigation of the CIA model can be expected to yield important information that can be used to better understand its human counterparts.