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通过固定在特异性抗体滤膜上的合成A抗原去除单克隆抗A抗体

Monoclonal anti-A antibody removal by synthetic A antigen immobilized on specific antibody filters.

作者信息

Gautam Shalini, Korchagina Elena Y, Bovin Nicolai V, Federspiel William J

机构信息

McGowan Institute for Regenerative Medicine, University of Pittsburgh, 215 McGowan Institute, 3025 East Carson Street, Pittsburgh, Pennsylvania 15203, USA.

出版信息

Biotechnol Bioeng. 2008 Mar 1;99(4):876-83. doi: 10.1002/bit.21621.

Abstract

Removal of blood group anti-A and anti-B antibodies can prevent hyperacute organ rejection in ABO-incompatible transplantation. We are developing an extracorporeal-specific antibody filter (SAF) as an immunoadsorption device for direct removal of ABO blood group antibodies from whole blood, without the need for plasma separation and plasma exchange. A hollow fiber-based small scale SAF (mini-SAF) device was fabricated and synthetic A antigen, Atrisaccharide (Atri) conjugated to activated polyacrylic acid, was immobilized on the fiber lumen surface. Monoclonal antibody anti-A IgM were specifically removed up to 70% of initial antibodies using mini-SAF device. The monoclonal anti-A capture experiments on mini-SAF indicated that antibody removal relative to the initial concentration is independent of inlet concentration in the beginning; however, as the surface starts saturating with bound antibodies, removal becomes dependent on inlet concentration. No significant effect of flow rate on removal rate was observed. The radial diffusion and axial convection-based mathematical model developed for unsteady state antibody removal was in good agreement with the experimental data and showed that the antibody removal rate can be maximized by increasing the antibody-binding capacity of the SAF.

摘要

去除血型抗A和抗B抗体可预防ABO血型不相容移植中的超急性器官排斥反应。我们正在开发一种体外特异性抗体过滤器(SAF)作为免疫吸附装置,用于直接从全血中去除ABO血型抗体,而无需进行血浆分离和血浆置换。制备了一种基于中空纤维的小型SAF(微型SAF)装置,并将与活化聚丙烯酸偶联的合成A抗原三糖(Atri)固定在纤维内腔表面。使用微型SAF装置可特异性去除高达70%的初始单克隆抗A IgM抗体。微型SAF上的单克隆抗A捕获实验表明,相对于初始浓度的抗体去除在开始时与入口浓度无关;然而,随着表面开始被结合的抗体饱和,去除变得依赖于入口浓度。未观察到流速对去除率有显著影响。为非稳态抗体去除建立的基于径向扩散和轴向对流的数学模型与实验数据吻合良好,表明通过提高SAF的抗体结合能力可使抗体去除率最大化。

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