Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
J Autoimmun. 2014 Nov;54:51-9. doi: 10.1016/j.jaut.2014.06.003. Epub 2014 Jun 24.
Myasthenia Gravis (MG) is an organ-specific autoimmune disease. In high percentage of patients there are autoantibodies to the nicotinic acetylcholine receptor (AChR) that attack AChR on muscle cells at the neuromuscular junction, resulting in muscle weakness. Experimental Autoimmune Myasthenia Gravis (EAMG) is an experimental model disease for MG. EAMG is induced in several animal species by immunization with acetylcholine receptor (AChR), usually isolated from the electric organ of electric fish, which is a rich source for this antigen. Our lab has been involved for several decades in research of AChR and of EAMG. The availability of an experimental autoimmune disease that mimics in many aspects the human disease, provides an excellent model system for elucidating the immunological nature and origin of MG, for studying various existing treatment modalities and for attempting the development of novel treatment approaches. In this review in honor of Michael Sela and Ruth Arnon, we report first on our early pioneering contributions to research on EAMG. These include the induction of EAMG in several animal species, early attempts for antigen-specific treatment for EAMG, elicitation and characterization of monoclonal antibodies and anti-idiotypic antibodies, measuring humoral and cellular AChR-specific immune responses in MG patient and more. In the second part of the review we discuss more recent studies from our lab towards developing and testing novel treatment approaches for myasthenia. These include antigen-dependent treatments aimed at specifically abrogating the humoral and cellular anti-AChR responses, as well as immunomodulatory approaches that could be used either alone, or in conjunction with antigen-specific treatments, or alternatively, serve as steroid-sparing agents.
重症肌无力（MG）是一种器官特异性自身免疫性疾病。在很大比例的患者中，存在针对烟碱型乙酰胆碱受体（AChR）的自身抗体，这些抗体攻击神经肌肉接头处的肌肉细胞上的 AChR，导致肌肉无力。实验性自身免疫性重症肌无力（EAMG）是一种用于 MG 的实验模型疾病。通过用乙酰胆碱受体（AChR）免疫几种动物物种，可以诱导 EAMG，AChR 通常来自电鱼的电器官，这是该抗原的丰富来源。我们实验室几十年来一直致力于 AChR 和 EAMG 的研究。这种在许多方面模拟人类疾病的实验性自身免疫疾病，为阐明 MG 的免疫学性质和起源、研究各种现有治疗方法以及尝试开发新的治疗方法提供了一个极好的模型系统。在纪念 Michael Sela 和 Ruth Arnon 的这篇综述中，我们首先报告了我们早期在 EAMG 研究方面的开创性贡献。这些贡献包括在几种动物物种中诱导 EAMG、早期尝试针对 EAMG 的抗原特异性治疗、诱导和表征单克隆抗体和抗独特型抗体、测量 MG 患者的体液和细胞 AChR 特异性免疫反应等。在综述的第二部分，我们讨论了我们实验室最近针对开发和测试新的治疗方法进行的研究，这些方法包括旨在特异性消除体液和细胞抗 AChR 反应的抗原依赖性治疗，以及可单独使用或与抗原特异性治疗结合使用的免疫调节方法，或者作为类固醇节省剂。
