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首页> 外文期刊>The FEBS journal >Exposure of IgG to an acidic environment results in molecular modifications and in enhanced protective activity in sepsis
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Exposure of IgG to an acidic environment results in molecular modifications and in enhanced protective activity in sepsis

机译：将IgG暴露在酸性环境中会导致分子修饰并增强败血症的保护活性

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摘要

IgG molecules are exposed on a regular basis to acidic conditions during immunoaffinity purification procedures, as well as during the production of some therapeutic immunoglobulin preparations. This exposure is known to induce in them an antigen-binding polyreactivity. The molecular mechanisms and the possible biological significance of this phenomenon remain, however, poorly understood. In addition to the previously reported ability of these modified IgG antibodies to interact with a large panel of self-antigens, enhanced binding to non-self-antigens (bacterial), an increased ability to engage in F(abo)/F(abo) (idiotype/anti-idiotype) interactions and an increased functional antigen-binding affinity are reported here. The newly acquired 'induced polyreactivity' of low-pH buffer-exposed IgG is related to structural changes in the immunoglobulin molecules, and is at least partly attributable to the enhanced role of the hydrophobic effect in their interactions with antigen. Our results suggest that data from many previous studies on monoclonal and polyclonal IgG antibodies purified by low-pH buffer elution from protein A or protein G immunoaffinity columns should be reconsidered, as the procedure itself may have dramatically affected their antigen-binding behavior and biological activity. Low-pH buffer-treated pooled therapeutic immunoglobulins acquire novel beneficial properties, as passive immunotherapy with the pH 4.0 buffer-exposed, but not with the native therapeutic intravenous immunoglobulin preparation, improves the survival of mice with bacterial lipopolysaccharide-induced septic shock.
机译：在免疫亲和纯化程序以及某些治疗性免疫球蛋白制剂的生产过程中，定期将IgG分子暴露于酸性条件下。已知这种暴露在其中诱导抗原结合多反应性。但是，这种现象的分子机制和可能的生物学意义仍然知之甚少。除了先前报道的这些修饰的IgG抗体与大量自身抗原相互作用的能力，与非自身抗原（细菌）的结合增强，参与F（abo）/ F（abo）的能力增强之外， （独特型/抗独特型）相互作用和增加的功能性抗原结合亲和力在这里报道。低pH缓冲液暴露的IgG的新获得的“诱导的多反应性”与免疫球蛋白分子的结构变化有关，并且至少部分归因于疏水作用在其与抗原相互作用中的增强作用。我们的结果表明，应重新考虑以前的许多关于通过低pH缓冲液从蛋白A或蛋白G免疫亲和柱纯化的单克隆和多克隆IgG抗体的研究数据，因为该过程本身可能会极大地影响其抗原结合行为和生物学活性。低pH缓冲液处理的合并治疗性免疫球蛋白具有新颖的有益特性，因为暴露于pH 4.0缓冲液的被动免疫疗法可提高细菌脂多糖诱导的败血性休克小鼠的存活率，而被动免疫疗法则不使用天然治疗性静脉注射免疫球蛋白制剂。

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