Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS
Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS
复制标题
DOI：
10.3389/fimmu.2020.01120
复制
发表时间：
2020-06-05
影响因子：
7.3
通讯作者：
Walz, Brigitte
中科院分区：
文献类型：
--
作者：
Fierz, Walter;Walz, Brigitte
人类冠状病毒（HCoV）是全世界呼吸道感染的最常见原因之一。迄今为止，在 SARS-CoV-2 大流行的发展过程中观察到的两个现象值得进一步关注。首先，儿童相对缺乏感染的临床症状，其次，某些患者早期出现 IgG。从免疫系统生理学的角度来看，当存在对交叉反应抗原的记忆时（通常是由于早期感染冠状病毒），二次免疫反应中预计会出现这种早期的特异性 IgG 升高。实际上，免疫系统对其已知的信息做出反应是典型的，这种现象在许多密切相关的病毒感染中观察到，被称为“原始抗原原罪”。那么问题就出现了，这种交叉反应抗体是否对新病毒具有保护作用。最糟糕的情况是，这种针对相关冠状病毒的交叉反应记忆抗体不仅没有保护作用，甚至会加剧感染和临床过程。这种抗体依赖性增强（ADE）现象已经在几种病毒感染中得到描述。因此，在 COVID-19 过程中针对 SARS-CoV-2 的 IgG 的产生可能并不是病毒清除和形成针对病毒的保护作用的简单标志。相反，由于与早期感染相关冠状病毒株的交叉反应，在某些患者中，IgG 可能会促进 ADE 导致的临床进展。患者的冠状病毒感染病毒史可能对当前 SARS-CoV-2 感染的发展至关重要。此外，在使用恢复期血清治疗 COVID-19 患者时需要注意。
Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed "original antigenic sin." The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.