Laboratory of Human Genetics of Infectious Diseases, Necker Branch, Institut National de la Santé et de la Recherche Médicale U1163, Necker Hospital for Sick Children, Paris, France.
University of Paris, Imagine Institute, Paris, France.
J Exp Med. 2021 Jul 5;218(7). doi: 10.1084/jem.20210554.
Patients with biallelic loss-of-function variants of AIRE suffer from autoimmune polyendocrine syndrome type-1 (APS-1) and produce a broad range of autoantibodies (auto-Abs), including circulating auto-Abs neutralizing most type I interferons (IFNs). These auto-Abs were recently reported to account for at least 10% of cases of life-threatening COVID-19 pneumonia in the general population. We report 22 APS-1 patients from 21 kindreds in seven countries, aged between 8 and 48 yr and infected with SARS-CoV-2 since February 2020. The 21 patients tested had auto-Abs neutralizing IFN-α subtypes and/or IFN-ω; one had anti-IFN-β and another anti-IFN-ε, but none had anti-IFN-κ. Strikingly, 19 patients (86%) were hospitalized for COVID-19 pneumonia, including 15 (68%) admitted to an intensive care unit, 11 (50%) who required mechanical ventilation, and four (18%) who died. Ambulatory disease in three patients (14%) was possibly accounted for by prior or early specific interventions. Preexisting auto-Abs neutralizing type I IFNs in APS-1 patients confer a very high risk of life-threatening COVID-19 pneumonia at any age.
患有 AIRE 双等位基因功能丧失变异的患者患有自身免疫性多内分泌腺综合征 1 型 (APS-1)，并产生广泛的自身抗体 (auto-Abs)，包括中和大多数 I 型干扰素 (IFN) 的循环自身抗体。这些自身抗体最近被报道至少占普通人群中危及生命的 COVID-19 肺炎病例的 10%。我们报告了来自七个国家的 21 个家系的 22 名 APS-1 患者，年龄在 8 至 48 岁之间，自 2020 年 2 月以来感染了 SARS-CoV-2。21 名接受检测的患者均具有中和 IFN-α亚型和/或 IFN-ω的自身抗体；一名患者具有抗 IFN-β抗体，另一名患者具有抗 IFN-ε抗体，但均无抗 IFN-κ抗体。值得注意的是，19 名患者 (86%) 因 COVID-19 肺炎住院，其中 15 名 (68%) 入住重症监护病房，11 名 (50%) 需要机械通气，4 名 (18%) 死亡。三名患者 (14%) 的门诊疾病可能归因于先前或早期的特定干预措施。任何年龄患有 APS-1 的患者体内预先存在的中和 I 型 IFN 的自身抗体使他们面临危及生命的 COVID-19 肺炎的极高风险。
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