Pharmazentrum Frankfurt/ZAFES, Goethe University Hospital, Frankfurt am Main, Germany.
Biochim Biophys Acta Mol Basis Dis. 2019 May 1;1865(5):970-981. doi: 10.1016/j.bbadis.2018.05.017. Epub 2018 May 29.
Many animal models for autoimmune hepatitis (AIH) have been described in the past. Most models had to deal with the relative immunosuppressive environment of the liver. Therefore, some models used a combination of several triggering factors often on a susceptible background to generate an aggressive immune response that targets the liver. In addition, in order to be able to track the immune response the models used specific model autoantigens as targets that are either not present or have not been identified as a natural autoantigen in AIH patients. Thereby the feasibility of such models is somewhat questionable. Although many historic approaches included challenges of experimental animals with liver homogenates it was only in the last decade that natural occurring liver autoantigens have been used in animal models. This article reflects on the requirements for breaking liver tolerance and on how an ideal experimental model for AIH would look like. In addition, it discusses historic as well as recent animal models in the context of feasibility of induction, similarity of the clinical outcome to human AIH, and gain of knowledge for possible future therapies.
过去已经描述了许多自身免疫性肝炎 (AIH) 的动物模型。大多数模型都必须应对肝脏相对免疫抑制的环境。因此,一些模型使用几种触发因素的组合,通常在易感背景下产生针对肝脏的侵袭性免疫反应。此外,为了能够跟踪免疫反应,模型使用了特定的模型自身抗原作为靶标,这些靶标在 AIH 患者中要么不存在,要么尚未被确定为天然自身抗原。因此,这些模型的可行性有些值得怀疑。尽管许多历史方法包括用肝匀浆挑战实验动物,但直到最近十年,天然存在的肝自身抗原才被用于动物模型。本文探讨了打破肝脏耐受的要求,以及理想的 AIH 实验模型应该是什么样子。此外,它还讨论了历史和最近的动物模型,涉及诱导的可行性、与人类 AIH 的临床结果的相似性,以及为可能的未来治疗方法获得知识。