首页> 外文期刊>Journal of Neuroimmunology: Official Bulletin of the Research Committee on Neuroimmunology of the World Federation of Neurology >Prevention of passively transferred experimental autoimmune myasthenia gravis by Fab fragments of monoclonal antibodies directed against the main immunogenic region of the acetylcholine receptor.
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Prevention of passively transferred experimental autoimmune myasthenia gravis by Fab fragments of monoclonal antibodies directed against the main immunogenic region of the acetylcholine receptor.

机译:通过针对乙酰胆碱受体主要免疫原性区域的单克隆抗体的Fab片段预防被动转移的实验性自身免疫性重症肌无力。

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摘要

The muscle acetylcholine receptor loss, responsible for the clinical symptoms of myasthenia gravis, is due mainly to mechanisms dependent on the bivalent character of the anti-receptor antibodies. In cell culture, univalent Fab fragments of monoclonal antibodies (mAbs) directed against the main immunogenic region (MIR) of the acetylcholine receptor are able to protect the receptor against the action of the intact antibodies. To investigate the potential therapeutic use of this approach, we examined the ability of the Fab fragment of anti-MIR mAb195 (Fab195) to protect the receptor in vivo against two anti-MIR mAbs. Because of the rapid clearance of Fab fragments from the circulation, Lewis rats were treated repeatedly with Fab195. The Fab fragment significantly protected muscle receptors against antibody-mediated loss and was very efficient in providing protection against clinical symptoms when its administration was commenced before, simultaneously with, or 2 h after, mAb injection. Twenty-four hours after mAb injection, the protected rats only showed mild myasthenic symptoms, whereas those which only received intact antibodies were moribund or dead. These results suggest that, once modified to ensure their low immunogenicity and a long half-life, anti-MIR Fab fragments might be useful in the specific immunotherapy of myasthenia gravis.
机译:导致重症肌无力临床症状的肌肉乙酰胆碱受体丢失,主要是由于依赖于抗受体抗体的二价特征的机制所致。在细胞培养中,针对乙酰胆碱受体主要免疫原性区域(MIR)的单克隆抗体(mAb)的单价Fab片段能够保护该受体免受完整抗体的作用。为了研究这种方法的潜在治疗用途,我们检查了抗MIR mAb195的Fab片段(Fab195)体内保护受体抵抗两种抗MIR mAb的能力。由于Fab片段从循环中快速清除,因此用Fab195反复治疗Lewis大鼠。 Fab片段在mAb注射之前,同时或之后2小时开始给药时,可显着保护肌肉受体免受抗体介导的损失,并且非常有效地提供针对临床症状的保护。 mAb注射后二十四小时,受保护的大鼠仅表现出轻度的肌无力症状,而仅接受完整抗体的大鼠则濒死或死亡。这些结果表明,一旦对其进行修饰以确保其低免疫原性和长半衰期,抗MIR Fab片段可能在重症肌无力的特异性免疫治疗中有用。

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