当前位置: X-MOL 学术bioRxiv. Immunol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
An Autoantigen Atlas from Human Lung HFL1 Cells Offers Clues to Neurological and Diverse Autoimmune Manifestations of COVID-19
bioRxiv - Immunology Pub Date : 2021-01-24 , DOI: 10.1101/2021.01.24.427965
Julia Y. Wang , Wei Zhang , Michael W. Roehrl , Victor B. Roehrl , Michael H. Roehrl

COVID-19 is accompanied by a myriad of both transient and long-lasting autoimmune responses. Dermatan sulfate (DS), a glycosaminoglycan crucial for wound healing, has unique affinity for autoantigens (autoAgs) from apoptotic cells. DS-autoAg complexes are capable of stimulating autoreactive B cells and autoantibody production. Using DS affinity, we identified an autoantigenome of 408 proteins from human fetal lung fibroblast HFL11 cells, at least 231 of which are known autoAgs. Comparing with available COVID data, 352 proteins of the autoantigenome have thus far been found to be altered at protein or RNA levels in SARS-Cov-2 infection, 210 of which are known autoAgs. The COVID-altered proteins are significantly associated with RNA metabolism, translation, vesicles and vesicle transport, cell death, supramolecular fibrils, cytoskeleton, extracellular matrix, and interleukin signaling. They offer clues to neurological problems, fibrosis, smooth muscle dysfunction, and thrombosis. In particular, 150 altered proteins are related to the nervous system, including axon, myelin sheath, neuron projection, neuronal cell body, and olfactory bulb. An association with the melanosome is also identified. The findings from our study illustrate a strong connection between viral infection and autoimmunity. The vast number of COVID-altered proteins with propensity to become autoAgs offers an explanation for the diverse autoimmune complications in COVID patients. The variety of autoAgs related to mRNA metabolism, translation, and vesicles raises concerns about potential adverse effects of mRNA vaccines. The COVID autoantigen atlas we are establishing provides a detailed molecular map for further investigation of autoimmune sequelae of the pandemic.

中文翻译:

来自人肺HFL1细胞的自身抗原图谱为COVID-19的神经学和多样的自身免疫表现提供线索

COVID-19伴随着无数的瞬时和长期自身免疫反应。硫酸皮肤素(DS)是一种对伤口愈合至关重要的糖胺聚糖,对来自凋亡细胞的自身抗原(autoAgs)具有独特的亲和力。DS-autoAg复合物能够刺激自身反应性B细胞和自身抗体的产生。使用DS亲和力,我们从人胎儿肺成纤维细胞HFL11细胞中鉴定了408种蛋白质的自身抗原组,其中至少231种是已知的自身Ag。与现有的COVID数据相比,迄今为止,发现SARS-Cov-2感染中有352种自身抗原组蛋白在蛋白质或RNA水平发生了改变,其中210种是已知的自身Ag。改变COVID的蛋白质与RNA代谢,翻译,囊泡和囊泡运输,细胞死亡,超分子原纤维,细胞骨架,细胞外基质和白介素信号传导。它们为神经系统疾病,纤维化,平滑肌功能障碍和血栓形成提供了线索。特别是,150种改变的蛋白质与神经系统有关,包括轴突,髓鞘,神经元投射,神经元细胞体和嗅球。还确定了与黑素体的关联。我们的研究结果表明,病毒感染与自身免疫之间存在密切的联系。大量易成为autoAgs的改变COVID的蛋白质为COVID患者的多种自身免疫并发症提供了解释。与mRNA代谢,翻译和囊泡有关的多种autoAg引起了人们对mRNA疫苗潜在副作用的担忧。
更新日期:2021-01-25
down
wechat
bug