抗独特型抗体与自身抗体。

Ann N Y Acad Sci. 1983;418:363-78. doi: 10.1111/j.1749-6632.1983.tb18086.x.

In this paper, we have provided experimental evidence that antibodies to autoantigens bear common idiotypes and that this property makes them susceptible to anti-idiotypic regulation. Spontaneously occurring autoantibodies to Tg in rats have been extensively investigated as a model of immune response responsible for the appearance of autoimmune disease. Large idiotypic cross-reactivity was found among autoantibodies of various individual animals. Similarly, a high degree of idiotypic relatedness was found among mouse monoclonal antibodies reacting with a highly conserved antigenic domain of thyroglobulin. Both rat and mice idiotype were found to be present on spontaneous and induced antibodies to rat thyroglobulin from individuals of other species. In vivo experiments showed that anti-idiotypic antibodies can be effective in suppressing autoantibodies formation. In the induced TIN in BN rats, a single injection of anti-idiotypic serum prior to the induction of autoimmune disease was sufficient to generate a significant selective suppression of autoantibodies produced against a pathogenetic chemical form of the autoantigen, that is, the one against which the autoantibodies used to prepare the anti-idiotypic reagent as mostly reactive. Similarly, it was found that repeated injections of anti-idiotype into rats with ongoing spontaneous production of autoantibodies to thyroglobulin were able to significantly decrease the amount of circulating autoantibodies from the pretreatment values. Thus, although the beneficial effect of anti-idiotype observed in these experiments was only partial, indications were obtained that a specific anti-idiotypic immunity can be used to regulate autoantibody production. Finally, evidence has been provided to support the hypothesis that auto-anti-idiotype, as a normal constituent of the immune response, can be responsible for the potentiation of immune complex-mediated tissue injury that is often the hallmark of autoimmune diseases.

在本文中，我们提供了实验证据，表明自身抗原抗体具有共同的独特型，且这一特性使其易于受到抗独特型调节。大鼠中针对甲状腺球蛋白（Tg）的自发产生的自身抗体已作为导致自身免疫性疾病出现的免疫反应模型进行了广泛研究。在各种个体动物的自身抗体中发现了大量独特型交叉反应性。同样，在与甲状腺球蛋白高度保守的抗原结构域反应的小鼠单克隆抗体中也发现了高度的独特型相关性。在来自其他物种个体的针对大鼠甲状腺球蛋白的自发和诱导抗体上均发现了大鼠和小鼠的独特型。体内实验表明，抗独特型抗体可有效抑制自身抗体的形成。在BN大鼠诱导的实验性自身免疫性甲状腺炎（TIN）中，在自身免疫性疾病诱导之前单次注射抗独特型血清足以对针对自身抗原致病化学形式产生的自身抗体产生显著的选择性抑制，即针对用于制备抗独特型试剂的自身抗体最具反应性的那种化学形式。同样，发现向正在自发产生针对甲状腺球蛋白自身抗体的大鼠反复注射抗独特型抗体能够使循环自身抗体量从预处理值显著降低。因此，尽管在这些实验中观察到的抗独特型的有益作用只是部分的，但有迹象表明特定的抗独特型免疫可用于调节自身抗体的产生。最后，已提供证据支持自身抗独特型作为免疫反应的正常组成部分可导致免疫复合物介导的组织损伤增强这一假说，而这种损伤通常是自身免疫性疾病的标志。