A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells

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• 作者：Masayuki Homma ; Akiyuki Uzawa ; Hitoshi Tanaka ; Naoki Kawaguchi…
• 关键词：AChR ; Fc ; Myasthenia gravis ; Anti ; AChR antibody ; Neutralization ; ADCC
• 刊名：Neurotherapeutics
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：14
• 期：1
• 页码：191-198
• 全文大小：
• 刊物主题：Neurosciences; Neurology; Neurosurgery; Neurobiology;
• 出版者：Springer US
• ISSN：1878-7479
• 卷排序：14

文摘

Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG. The effects of AChR-Fc in vivo were also examined using rat MG models. AChR-Fc bound to anti-AChR antibodies and exhibited cytotoxicity against patient-derived antibody-producing B cells. Additionally, a dose-dependent improvement in the clinical signs of disease was observed in a rat MG model. AChR-Fc can diminish signs of MG by neutralizing anti-AChR antibodies and enhancing cytotoxicity against autoantibody-producing B cells. Thus, AChR-Fc can be a novel therapeutic biomolecule for patients with MG.