Department of Immunology, Labor Berlin GmbH, Berlin, Germany.
Institute of Medical Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
J Clin Invest. 2021 Jul 15;131(14). doi: 10.1172/JCI150867.
Autoantibodies against IFN-α and IFN-ω (type I IFNs) were recently reported as causative for severe COVID-19 in the general population. Autoantibodies against IFN-α and IFN-ω are present in almost all patients with autoimmune polyendocrine syndrome type 1 (APS-1) caused by biallelic deleterious or heterozygous dominant mutations in AIRE. We therefore hypothesized that autoantibodies against type I IFNs also predispose patients with APS-1 to severe COVID-19. We prospectively studied 6 patients with APS-1 between April 1, 2020 and April 1, 2021. Biobanked pre-COVID-19 sera of APS-1 subjects were tested for neutralizing autoantibodies against IFN-α and IFN-ω. The ability of the patients' sera to block recombinant human IFN-α and IFN-ω was assessed by assays quantifying phosphorylation of signal transducer and activator of transcription 1 (STAT1) as well as infection-based IFN-neutralization assays. We describe 4 patients with APS-1 and preexisting high titers of neutralizing autoantibodies against IFN-α and IFN-ω who contracted SARS-CoV-2, yet developed only mild symptoms of COVID-19. None of the patients developed dyspnea, oxygen requirement, or high temperature. All infected patients with APS-1 were females and younger than 26 years of age. Clinical penetrance of neutralizing autoantibodies against type I IFNs for severe COVID-19 is not complete.
自身抗体针对 IFN-α 和 IFN-ω（I 型干扰素）最近被报道为导致普通人群中严重 COVID-19 的原因。自身抗体针对 IFN-α 和 IFN-ω 存在于几乎所有由 AIRE 双等位基因有害或杂合显性突变引起的自身免疫性多内分泌综合征 1 型（APS-1）患者中。因此，我们假设 I 型干扰素的自身抗体也使 APS-1 患者易患严重的 COVID-19。我们前瞻性地研究了 2020 年 4 月 1 日至 2021 年 4 月 1 日期间的 6 名 APS-1 患者。APS-1 患者的生物银行 COVID-19 前血清用于检测针对 IFN-α 和 IFN-ω 的中和自身抗体。通过定量测定信号转导和转录激活因子 1（STAT1）磷酸化以及基于感染的 IFN 中和测定来评估患者血清阻断重组人 IFN-α 和 IFN-ω 的能力。我们描述了 4 名 APS-1 患者，他们在感染 SARS-CoV-2 之前存在针对 IFN-α 和 IFN-ω 的高滴度中和自身抗体，但仅出现轻度 COVID-19 症状。没有患者出现呼吸困难、需要氧气或高温。所有感染 APS-1 的患者均为女性且年龄小于 26 岁。中和自身抗体针对 I 型干扰素的严重 COVID-19 的临床通透性并不完全。
