National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation, Oparina Street 4, 117997 Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Moscow, Russia.
Viruses. 2023 Jul 20;15(7):1584. doi: 10.3390/v15071584.
Antibody-dependent enhancement (ADE) is a phenomenon where virus-specific antibodies paradoxically cause enhanced viral replication and/or excessive immune responses, leading to infection exacerbation, tissue damage, and multiple organ failure. ADE has been observed in many viral infections and is supposed to complicate the course of COVID-19. However, the evidence is insufficient. Since no specific laboratory markers have been described, the prediction and confirmation of ADE are very challenging. The only possible predictor is the presence of already existing (after previous infection) antibodies that can bind to viral epitopes and promote the disease enhancement. At the same time, the virus-specific antibodies are also a part of immune response against a pathogen. These opposite effects of antibodies make ADE research controversial. The assignment of immunoglobulins to ADE-associated or virus neutralizing is based on their affinity, avidity, and content in blood. However, these criteria are not clearly defined. Another debatable issue (rather terminological, but no less important) is that in most publications about ADE, all immunoglobulins produced by the immune system against pathogens are qualified as pre-existing antibodies, thus ignoring the conventional use of this term for natural antibodies produced without any stimulation by pathogens. Anti-glycan antibodies (AGA) make up a significant part of the natural immunoglobulins pool, and there is some evidence of their antiviral effect, particularly in COVID-19. AGA have been shown to be involved in ADE in bacterial infections, but their role in the development of ADE in viral infections has not been studied. This review focuses on pros and cons for AGA as an ADE trigger. We also present the results of our pilot studies, suggesting that AGAs, which bind to complex epitopes (glycan plus something else in tight proximity), may be involved in the development of the ADE phenomenon.
抗体依赖的增强作用（ADE）是一种现象，即病毒特异性抗体反常地导致病毒复制增强和/或过度免疫反应，导致感染恶化、组织损伤和多器官衰竭。ADE 已在许多病毒感染中观察到，据推测会使 COVID-19 的病程复杂化。然而，证据并不充分。由于尚未描述特定的实验室标志物，因此预测和确认 ADE 非常具有挑战性。唯一可能的预测因子是存在先前感染后已存在的（先前感染后已存在的）抗体，这些抗体可以与病毒表位结合并促进疾病增强。同时，病毒特异性抗体也是针对病原体的免疫反应的一部分。抗体的这些相反作用使得 ADE 研究具有争议性。将免疫球蛋白分配给与 ADE 相关或具有中和病毒作用的免疫球蛋白是基于它们的亲和力、亲合力和血液中的含量。然而，这些标准没有明确定义。另一个有争议的问题（更确切地说是术语问题，但同样重要）是，在大多数关于 ADE 的出版物中，免疫系统针对病原体产生的所有免疫球蛋白都被定性为预先存在的抗体，从而忽略了该术语的传统用途，即用于在没有任何病原体刺激的情况下产生的天然抗体。糖结合抗体（AGA）构成天然免疫球蛋白库的重要组成部分，并且有一些证据表明它们具有抗病毒作用，特别是在 COVID-19 中。AGA 已被证明参与细菌感染中的 ADE，但它们在病毒感染中 ADE 发展中的作用尚未得到研究。本综述重点介绍 AGA 作为 ADE 触发因素的利弊。我们还介绍了我们的初步研究结果，表明与复杂表位（糖加上紧密接近的其他物质）结合的 AGAs 可能参与 ADE 现象的发展。
