I型IFN免疫的先天错误与致命性COVID-19相关
作者：小柯机器人 发布时间：2020/9/26 10:09:23
美国洛克菲勒大学Jean-Laurent Casanova等研究人员合作发现I型IFN免疫的先天错误与致命性COVID-19相关。2020年9月24日，《科学》杂志在线发表了这一成果。
相对于534名无症状或良性感染的受试者，研究人员在659名威胁生命的COVID-19肺炎患者中发现了13个人类基因座上预测为功能丧失（LOF）的罕见变体富集，这些基因座已知参与调控TLR3-和IRF7依赖型I型干扰素（IFN）对流感病毒的免疫。通过在这13个基因座上测试这些和其他罕见的变异，研究人员实验性地定义了23例（3.5%）LOF变异，年龄在17至77岁之间，这些变异隐藏在常染色体隐性或显性缺陷背后。
研究人员发现人类成纤维细胞的突变影响了这一途径，从而很容易感染SARS-CoV-2。先天性TLR3和IRF7依赖的I型IFN免疫错误可能是既往无严重感染患者发生致命性COVID-19肺炎的基础。
据了解，感染SARS-CoV-2的临床结果可从无症状感染到致命。
附：英文原文
Title:Inborn errors of type I IFN immunity in patients with life-threatening COVID-19
Author:Qian Zhang1, Paul Bastard2,3,*, Zhiyong Liu1,*, Jérémie Le Pen4,*, Marcela Moncada-Velez
Issue&Volume:24 Sep 2020
Abstract: Clinical outcome upon infection with SARS-CoV-2 ranges from silent infection to lethal COVID-19. We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern TLR3- and IRF7-dependent type I interferon (IFN) immunity to influenza virus, in 659 patients with life-threatening COVID-19 pneumonia, relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally define LOF variants in 23 patients (3.5%), aged 17 to 77 years, underlying autosomal recessive or dominant deficiencies. We show that human fibroblasts with mutations affecting this pathway are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection.
DOI:DOI: 10.1126/science.abd4570
Source: https://science.sciencemag.org/content/early/2020/09/23/science.abd4570
期刊信息
Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：41.037