Center of Molecular Biology and Biomedicine, Institute of Biology and Biomedicine, National Research Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave, Nizhny Novgorod 603022, Russian Federation.
Centre de Recherche des Cordeliers, INSERM, CNRS, Sorbonne Université, Université de Paris, 15 Rue de l'École de Médecine, 75006 Paris, France.
Immunobiology. 2022 May;227(3):152213. doi: 10.1016/j.imbio.2022.152213. Epub 2022 Apr 6.
Previous studies have shown that polyreactive antibodies play an important role in the frontline defense against the dissemination of pathogens in the pre-immune host. Interestingly, antigen-binding polyreactivity can not only be inherent, but also acquired post-translationally. The ability of individual monoclonal IgG and IgE antibodies to acquire polyreactivity following contact with various agents that destabilize protein structure (urea, low pH) or have a pro-oxidative potential (heme, ferrous ions) has been studied in detail. However, to the best of our knowledge this property of human IgA has previously been described only cursorily. In the present study pooled human serum IgA and two human monoclonal IgA antibodies were exposed to buffers with acidic pH, to free heme or to ferrous ions, and the antigen-binding behavior of the native and modified IgA to viral and bacterial antigens were compared using immunoblot and ELISA. We observed a dose-dependent increase in reactivity to several bacterial extracts and to pure viral antigens. This newly described property of IgA may have therapeutic potential as has already been shown for pooled IgG with induced polyreactivity.
先前的研究表明，多反应性抗体在无免疫宿主中抵御病原体传播的一线防御中发挥着重要作用。有趣的是，抗原结合的多反应性不仅可以是固有存在的，也可以是翻译后获得的。已经详细研究了个体单克隆 IgG 和 IgE 抗体在接触各种破坏蛋白质结构的试剂（尿素、低 pH 值）或具有促氧化潜能的试剂（血红素、亚铁离子）后获得多反应性的能力。然而，据我们所知，人类 IgA 的这种特性以前只是粗略描述过。在本研究中，我们将人血清 IgA 池和两种人源单克隆 IgA 抗体暴露于酸性 pH 值的缓冲液中、游离血红素或亚铁离子中，并使用免疫印迹和 ELISA 比较了天然和修饰的 IgA 对病毒和细菌抗原的抗原结合行为。我们观察到对几种细菌提取物和纯病毒抗原的反应性呈剂量依赖性增加。这种新描述的 IgA 特性可能具有治疗潜力，正如已经显示的那样，诱导多反应性的 IgG 池具有治疗潜力。
