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Anticomplementary activity of horse IgG and F(ab')2 antivenoms

机译:马IgG和F(ab')2抗蛇毒素的抗互补活性

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摘要

Envenomation by poisonous animals is a neglected condition according to the World Health Organization (WHO). Antivenoms are included in the WHO Essential Medicines List. It has been assumed that immunoglobulin G (IgG) antivenoms could activate the complement system through Fc and induce early adverse reactions (EARs). However, data in the literature indicate that F(ab')2 fragments can also activate the complement system. Herein, we show that several batches of IgG and F(ab')2 antivenoms from the Butantan, Vital Brazil, and Clodomiro Picado Institutes activated the complement classical pathway and induced the production of C3a; however, only those antivenoms from Clodomiro Picado generated C5a. Different protein profiles (IgG heavy chain, protein contaminants, and aggregates) were observed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot analyses. Our results show that various antivenoms from different producers are able to activate the classical pathway of the complement system and generate anaphylatoxins, and these findings suggest that factors, such as composition, contaminant proteins, and aggregates, may influence the anticomplementary activity of antivenoms in vitro. Therefore, there is a need to further improve antivenom production methods to reduce their anticomplementary activity and potential to cause EARs.
机译:根据世界卫生组织(WHO)的说法,有毒动物的毒化是一种被忽视的条件。抗毒剂已包含在WHO的基本药物清单中。已经假定免疫球蛋白G(IgG)抗蛇毒血清可通过Fc激活补体系统并诱导早期不良反应(EARs)。但是,文献中的数据表明F(ab')2片段也可以激活补体系统。本文中,我们显示了来自Butantan,Vital Brazil和Clodomiro Picado研究所的几批IgG和F(ab')2抗蛇毒血清激活了补体经典途径并诱导了C3a的产生。但是,只有Clodomiro Picado中的那些抗蛇毒血清产生了C5a。通过十二烷基硫酸钠聚丙烯酰胺凝胶电泳(SDS-PAGE)和Western印迹分析观察到不同的蛋白质谱(IgG重链,蛋白质污染物和聚集体)。我们的结果表明,来自不同生产者的各种抗蛇毒血清都能激活补体系统的经典途径并产生过敏毒素,这些发现表明,诸如成分,污染物蛋白和聚集体等因素可能会影响抗蛇毒血清的体外抗互补活性。 。因此,需要进一步改进抗蛇毒血清的生产方法,以降低其抗互补活性和引起EARs的潜力。

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