从罕见的免疫紊乱到常见的感染决定因素：追寻机制线索。
From rare disorders of immunity to common determinants of infection: Following the mechanistic thread.
机构信息
St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France; Paris Cité University, Imagine Institute, Paris, France; Department of Pediatrics, Necker Hospital for Sick Children, Paris, France; Howard Hughes Medical Institute, New York, NY, USA.
St Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY, USA; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM, Necker Hospital for Sick Children, Paris, France; Paris Cité University, Imagine Institute, Paris, France.
出版信息
Cell. 2022 Aug 18;185(17):3086-3103. doi: 10.1016/j.cell.2022.07.004.
The immense interindividual clinical variability during any infection is a long-standing enigma. Inborn errors of IFN-γ and IFN-α/β immunity underlying rare infections with weakly virulent mycobacteria and seasonal influenza virus have inspired studies of two common infections: tuberculosis and COVID-19. A TYK2 genotype impairing IFN-γ production accounts for about 1% of tuberculosis cases, and autoantibodies neutralizing IFN-α/β account for about 15% of critical COVID-19 cases. The discovery of inborn errors and mechanisms underlying rare infections drove the identification of common monogenic or autoimmune determinants of related common infections. This "rare-to-common" genetic and mechanistic approach to infectious diseases may be of heuristic value.
任何感染期间个体间的巨大临床变异性一直是一个谜。IFN-γ 和 IFN-α/β 免疫的先天性错误是导致罕见的弱毒分枝杆菌和季节性流感病毒感染的基础，这启发了对两种常见感染的研究：结核病和 COVID-19。一种导致 IFN-γ 产生受损的 TYK2 基因型约占结核病病例的 1%，而中和 IFN-α/β 的自身抗体约占严重 COVID-19 病例的 15%。罕见感染的先天性错误和机制的发现推动了对相关常见感染的常见单基因或自身免疫决定因素的鉴定。这种将罕见疾病转化为常见疾病的遗传和机制方法可能具有启发价值。
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