Chen Song1, Zhikai Xu2, Jianting Miao1, Jiang Xu1, Xingan Wu2, Fanglin Zhang2, Hong Lin1, Zhuyi Li1, Henry J Kaminski3. 1. Department of Neurology, Tangdu Hospital, Fourth Military Medical University, Xi'an, China. 2. Department of Microbiology, Fourth Military Medical University, Xi'an, China. 3. Department of Neurology, George Washington University, 2150 Pennsylvania Avenue NW, Suite 7-406, Washington, DC 20037, USA.
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.
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.
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