Butler Dorothy L, Gildersleeve Jeffrey C
Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702.
bioRxiv. 2020 Oct 16:2020.10.15.341479. doi: 10.1101/2020.10.15.341479.
SARS-CoV-2 is a deadly virus that is causing the global pandemic coronavirus disease 2019 (COVID-19). Our immune system plays a critical role in preventing, clearing, and treating the virus, but aberrant immune responses can contribute to deleterious symptoms and mortality. Many aspects of immune responses to SARS-CoV-2 are being investigated, but little is known about immune responses to carbohydrates. Since the surface of the virus is heavily glycosylated, pre-existing antibodies to glycans could potentially recognize the virus and influence disease progression. Furthermore, antibody responses to carbohydrates could be induced, affecting disease severity and clinical outcome. In this study, we used a carbohydrate antigen microarray with over 800 individual components to profile serum anti-glycan antibodies in COVID-19 patients and healthy control subjects. In COVID-19 patients, we observed abnormally high IgG and IgM antibodies to numerous self-glycans, including gangliosides, -linked glycans, LacNAc-containing glycans, blood group H, and sialyl Lewis X. Some of these anti-glycan antibodies are known to play roles in autoimmune diseases and neurological disorders, which may help explain some of the unusual and prolonged symptoms observed in COVID-19 patients. The detection of antibodies to self-glycans has important implications for using convalescent serum to treat patients, developing safe and effective SARS-CoV-2 vaccines, and understanding the risks of infection. In addition, this study provides new insight into the immune responses to SARS-CoV-2 and illustrates the importance of including host and viral carbohydrate antigens when studying immune responses to viruses.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是一种致命病毒，正引发全球大流行的2019冠状病毒病（COVID-19）。我们的免疫系统在预防、清除和治疗该病毒方面发挥着关键作用，但异常的免疫反应可能导致有害症状和死亡。针对SARS-CoV-2的免疫反应的许多方面正在研究中，但对碳水化合物的免疫反应了解甚少。由于该病毒表面高度糖基化，预先存在的针对聚糖的抗体可能会识别该病毒并影响疾病进展。此外，可能会诱导针对碳水化合物的抗体反应，影响疾病严重程度和临床结果。在本研究中，我们使用了一种包含800多种单个成分的碳水化合物抗原微阵列，来分析COVID-19患者和健康对照受试者血清中的抗聚糖抗体。在COVID-19患者中，我们观察到针对多种自身聚糖的IgG和IgM抗体异常升高，包括神经节苷脂、N-连接聚糖、含乳糖胺的聚糖、血型H和唾液酸化路易斯X。其中一些抗聚糖抗体已知在自身免疫性疾病和神经疾病中起作用，这可能有助于解释COVID-19患者中观察到的一些不寻常和持续的症状。检测针对自身聚糖的抗体对于使用康复期血清治疗患者、开发安全有效的SARS-CoV-2疫苗以及了解感染风险具有重要意义。此外，本研究为针对SARS-CoV-2的免疫反应提供了新的见解，并说明了在研究针对病毒的免疫反应时纳入宿主和病毒碳水化合物抗原的重要性。
