Kanduc Darja
Department of Biosciences, Biotechnologies, and Biopharmaceutics, University of Bari, 70125 Bari, Italy.
Antibodies (Basel). 2021 Sep 24;10(4):36. doi: 10.3390/antib10040036.
The aim of this study was to investigate the role of molecular mimicry in the cytokine storms associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Human proteins endowed with anti-inflammatory activity were assembled and analyzed for peptide sharing with the SARS-CoV-2 spike glycoprotein (gp) using public databases. It was found that the SARS-CoV-2 spike gp shares numerous pentapeptides with anti-inflammatory proteins that, when altered, can lead to cytokine storms characterized by diverse disorders such as systemic multiorgan hyperinflammation, macrophage activation syndrome, ferritinemia, endothelial dysfunction, and acute respiratory syndrome. Immunologically, many shared peptides are part of experimentally validated epitopes and are also present in pathogens to which individuals may have been exposed following infections or vaccinal routes and of which the immune system has stored memory. Such an immunologic imprint might trigger powerful anamnestic secondary cross-reactive responses, thus explaining the raging of the cytokine storm that can occur following exposure to SARS-CoV-2. In conclusion, the results support molecular mimicry and the consequent cross-reactivity as a potential mechanism in SARS-CoV-2-induced cytokine storms, and highlight the role of immunological imprinting in determining high-affinity, high-avidity, autoimmune cross-reactions as a pathogenic sequela associated with anti-SARS-CoV-2 vaccines.
本研究的目的是调查分子模拟在与严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关的细胞因子风暴中的作用。利用公共数据库，收集具有抗炎活性的人类蛋白质，并分析其与SARS-CoV-2刺突糖蛋白（gp）的肽段共享情况。研究发现，SARS-CoV-2刺突gp与抗炎蛋白共享大量五肽，这些五肽发生改变时可导致细胞因子风暴，其特征为多种病症，如全身性多器官过度炎症、巨噬细胞活化综合征、铁蛋白血症、内皮功能障碍和急性呼吸综合征。在免疫学上，许多共享肽是经过实验验证的表位的一部分，也存在于个体在感染或接种疫苗后可能接触过的病原体中，并且免疫系统已存储了对这些病原体的记忆。这种免疫印记可能会引发强大的回忆性二次交叉反应，从而解释了接触SARS-CoV-2后可能发生的细胞因子风暴的肆虐。总之，这些结果支持分子模拟以及随之而来的交叉反应是SARS-CoV-2诱导的细胞因子风暴的潜在机制，并强调了免疫印记在确定高亲和力、高亲合力的自身免疫交叉反应中的作用，这种交叉反应是与抗SARS-CoV-2疫苗相关的致病后遗症。
