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在严重的COVID-19中,针对尖端蛋白的受体结合域的原血栓抗体
Wen Zhu1,2, Yongwei Zheng1, Mei Yu1
1Versiti Blood Research Institute, Milwaukee, WI.
Blood
|November 22, 2024
概括
严重的COVID-19患者发展出针对SARS-CoV-2尖端蛋白的RBD的前血栓性抗体,类似于氨酸诱导的血栓性缺血 (HIT) 抗体,有助于血栓形成. 这些抗体激活血小板,与炎症和组织损伤相关.
科学领域:
- 免疫学 免疫学 免疫学
- 血液学 血液学 血液学
- 病毒学 病毒学
背景情况:
- 血栓塞栓并发症在严重的COVID-19中很常见.
- 研究的是类似于氨酸诱导的血栓缩 (HIT) 时的原血栓抗体.
- COVID-19患者表现出识别肝素和血小板因子4 (PF4) 复合体的抗体.
研究的目的:
- 在严重的COVID-19中调查前血栓抗体.
- 为了确定这些抗体是否与HIT抗体相似.
- 探索COVID-19中血栓形成的机制.
主要方法:
- 在130名住院COVID-19患者中分析IgG抗体.
- 对抗体诱导的血小板激活和P-选择因表达的评估.
- 克隆受体结合域 (RBD) 特定抗体并分析它们的序列.
主要成果:
- 80%的患者有PF4/H反应性IgG; 41%的患者有血小板激活抗体.
- 这些抗体存在不论对肝素的暴露,不像在HIT.
- PF4/H反应性IgG与向SARS-CoV-2尖端蛋白RBD的抗体相关.
- 特定于RBD的抗体激活了血小板,并且与致病性HIT抗体具有结构上的相似性.
- 在严重的COVID-19患者中发现了具有特定HCDR3签名的扩展B细胞.
结论:
- COVID-19 患者会产生功能性,RBD 特定的抗体,激活血小板.
- 这些抗体与HIT抗体具有共同的特征,表明一种新的血栓机制.
- 特定于RBD的抗体可能通过血小板激活和炎症导致COVID-19中的血栓形成.
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