scFv-DAF 融合蛋白对乙酰胆碱受体补体攻击的保护作用：治疗重症肌无力的一种可能选择。
Protective effect of scFv-DAF fusion protein on the complement attack to acetylcholine receptor: a possible option for treatment of myasthenia gravis.
机构信息
Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Department of Microbiology, Fourth Military Medical University, Xi'an, China.
出版信息
Muscle Nerve. 2012 May;45(5):668-675. doi: 10.1002/mus.23247.
Abstract
INTRODUCTION
Autoantibody-induced complement activation, which causes disruption of the postsynaptic membrane, is recognized as a key pathogenic factor in myasthenia gravis (MG). Therefore, specific targeting of complement inhibitors to the site of complement activation is a potential therapeutic strategy for treatment of MG.
METHODS
We assessed expression of single-chain antibody fragment-decay accelerating factor (scFv-DAF), comprising a single-chain fragment scFv1956 based on the rat complement inhibitor DAF in prokaryotic systems, and studied its inhibitory effect on complement deposition in vitro.
RESULTS
The recombinant conjugate scFv-DAF completely retained the wild-type binding activity of scFv1956 to AChR and inhibited complement activation of DAF in vitro.
CONCLUSIONS
We found that scFv-DAF could bind specifically to TE671 cells, and it is significantly more potent at inhibiting complement deposition than the untargeted parent molecule DAF. scFv-DAF may be a candidate for in vivo protection of the AChR in MG.
摘要
简介
自身抗体诱导的补体激活会破坏突触后膜，这被认为是重症肌无力 (MG) 的一个关键致病因素。因此，将补体抑制剂特异性靶向补体激活部位是治疗 MG 的一种潜在治疗策略。
方法
我们评估了单链抗体片段衰变加速因子 (scFv-DAF) 的表达，该片段由基于大鼠补体抑制剂 DAF 的原核系统中的单链片段 scFv1956 组成，并研究了其在体外对补体沉积的抑制作用。
结果
重组缀合物 scFv-DAF 完全保留了 scFv1956 对 AChR 的野生型结合活性，并在体外抑制了 DAF 的补体激活。
结论
我们发现 scFv-DAF 可以特异性结合 TE671 细胞，并且在抑制补体沉积方面比非靶向亲本分子 DAF 更有效。scFv-DAF 可能是体内保护 MG 中 AChR 的候选物。
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