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炎症风险通过抗ACKR1自身抗体促进COVID后内皮功能障碍

Ee-Soo Lee¹, Nhi Nguyen¹, Barnaby E Young^1,2,3,4

¹Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.

Life science alliance

|May 13, 2024

概括

COVID-19幸存者对非典型化学因受体1 (ACKR1) 的自身抗体呈高水平,与血管功能障碍和疾病有关. 这些自身抗体促进细胞损伤,这表明慢性炎症的新治疗点.

科学领域:

免疫学免疫学免疫学
血管生物学血管生物学
传染性疾病传染性疾病

背景情况:

亚临床血管功能障碍可能会随着COVID-19后持续的炎症而恶化.
自动抗体在COVID-19幸存者的血管功能障碍中的作用还没有得到充分研究.

研究的目的:

研究自身抗体,特别是抗ACKR1的患病率和对健康的COVID-19幸存者的血管功能障碍的影响.
探索抗ACKR1自身抗体与血管疾病结果之间的关联.
阐明这些自身抗体影响内皮细胞的机制.

主要方法:

对COVID-19幸存者的抗ACKR1自身抗体,系统性细胞因子和内皮细胞的分析.
针对血管疾病结果的独立队列的纵向随访.
单细胞转录组分析小鼠内皮细胞,以确定ACKR1表达模式.
使用从患者血中纯化的IgG在人静脉内皮细胞和外周血液单核细胞 (PBMCs) 上进行的功能测试.

主要成果:

COVID-19幸存者具有显著升高的抗ACKR1自身抗体,与细胞因子和内皮功能障碍相关.
这些自身抗体与长期随访队列中血管疾病增加有关.
ACKR1的表达在小鼠大脑和肌的静脉区域中得到了丰富.
患者IgG通过PBMC增强了抗体依赖的细胞毒性 (ADCC),而ACKR1阻断剂可以减轻这种毒性.

结论:

在COVID-19幸存者的抗ACKR1自身抗体增加有助于血管功能障碍和疾病.
针对ACKR1的自身抗体可能在COVID-19相关的静脉血栓塞栓症中发挥作用.
针对ACKR1自身抗体反应性的治疗策略可以缓解慢性血管炎症.

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