危及生命的COVID-19患者对I型IFN的自身抗体
Paul Bastard1,2,3, Lindsey B Rosen4, Qian Zhang3
1Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children, Paris, France. jean-laurent.casanova@rockefeller.edu paul.bastard@institutimagine.org.
Science (New York, N.Y.)
|September 25, 2020
概括
在超过10%的重症COVID-19患者,特别是男性中发现了对I型干扰素 (IFN) 的中和性自身抗体. 这种自身免疫反应解释了大量受影响个体的严重疾病.
科学领域:
- 免疫学
- 病毒学
- 遗传学
背景情况:
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 感染在临床结果中表现出显著的个体间差异.
- 了解导致2019年严重冠状病毒病 (COVID-19) 的宿主因素对于有效治疗至关重要.
研究的目的:
- 在危及生命的COVID-19肺炎患者中调查自身抗体对I型干扰素 (IFN) 的作用.
- 在不同患者群体和健康个体中确定这些自身抗体的患病率.
主要方法:
- 在危急的COVID-19患者中检测中和性免疫球蛋白G (IgG) 对干扰素-ω (IFN-ω) 和干扰素-α (IFN-α) 亚型的自身抗体.
- 在无症状或轻度SARS-CoV-2感染的个体和健康对照者中评估自身抗体的存在.
- 在体外测试以评估针对I型IFN的鉴定自抗体的中和能力.
主要成果:
- 在严重的COVID-19肺炎发作时,987名患者中有101名 (约10.2%) 具有针对I型IFN (IFN-ω,IFN-α或两者) 的中和性自身抗体.
- 在轻度或无症状的SARS-CoV-2感染者中,这些自身抗体在很大程度上不存在,而在健康人群中则很少出现.
- 鉴定到的自身抗体显示出能够在体外中中和I型IFN对SARS-CoV-2的抗病毒活性.
- 患有自身抗体的患者主要是男性 (101人中有95人),年龄在25岁至87岁之间.
结论:
- 一种I型干扰素免疫的B细胞自身免疫表现有助于至少2.6%的女性和12.5%的男性发生危及生命的COVID-19肺炎.
- 针对I型IFN的自身抗体的存在是严重COVID-19的一个重要因素,尤其是在老年男性中.
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