在严重的COVID-19中失调的原始B细胞和de novo自身反应性
Matthew C Woodruff1,2, Richard P Ramonell3, Natalie S Haddad4
1Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, GA, USA.
严重的COVID-19会触发原始B细胞的自身反应性抗体产生,从而导致自身反应性. 这种途径在康复后消失,但持续的自身反应可能与COVID后的情况有关.
科学领域:
- 免疫学
- 病毒学
- 自体免疫性
背景情况:
- 严重的SARS-CoV-2感染会导致显著的免疫激活.
- 在COVID-19中已经发现了自我反应性抗体的出现,但它们的起源和解决方案尚不清楚.
- 毛囊外B细胞激活,与慢性自身免疫的自身反应性抗体形成有关,是严重的COVID-19的一个特征.
研究的目的:
- 调查不同严重程度的COVID-19患者自身反应的起源,特征和解决方案.
- 确定与严重的SARS-CoV-2感染和随后的自身反应相关的特定B细胞群和抗体特征.
主要方法:
- 在轻度和重度COVID-19患者中分析单细胞B细胞谱.
- 对突变负载,选择压力和抗原特异性的抗体分泌细胞 (ASC) 的分析.
- 在急性感染和康复期间对血清自身反应的纵向评估.
主要成果:
- 在严重的COVID-19中,具有低选择性压力的天真衍生,低突变IgG1ASC的扩张.
- 症状出现后10 - 15天出现了对核抗原和碳amylated蛋白质的渐进性,广泛的自身反应.
- 针对SARS-CoV-2和自身抗原,包括致病性自身抗体的特定克隆型被确定.
- 这种自动反应途径在恢复时收缩,急性衍生ASC的损失.
- 在一些患有COVID后续症状的患者中观察到持续的血清自身反应.
结论:
- 严重的COVID-19会诱导一种独特的自动反应性B细胞反应,这种反应源自原始的前体.
- 在恢复过程中该途径的解决表明潜在的干预窗口.
- 持续的自身反应可能导致COVID后症状,需要进一步调查.
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