与抗 IFN-α 自身抗体相比，儿童的抗 IFN-ω 自身抗体与 COVID-19 肺炎风险增加相关。

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children.

机构信息

Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children , Paris, France.

University Paris Cité, Imagine Institute , Paris, France.

出版信息

J Exp Med. 2024 Feb 5;221(2). doi: 10.1084/jem.20231353. Epub 2024 Jan 4.

DOI:10.1084/jem.20231353

PMID:38175961

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10771097/

Abstract

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-α2 in 10 patients: IFN-α2 only in three, IFN-α2 plus IFN-ω in five, and IFN-α2, IFN-ω plus IFN-β in two; IFN-ω only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-α2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-ω in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-α2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-ω only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-ω and/or IFN-α2.

摘要

我们发现，在 183 名因 COVID-19 肺炎住院的未接种疫苗的儿童中，有 19 人（10.4%）存在中和 I 型干扰素（IFN-α2 的 10 例：仅 3 例 IFN-α2、5 例 IFN-α2+IFN-ω 和 2 例 IFN-α2、IFN-ω+IFN-β；仅 9 例 IFN-ω）的自身抗体（Abs）。7 名儿童（3.8%）的 Abs 中和至少 10ng/ml 的一种 IFN，而其他 12 名儿童（6.6%）的 Abs 仅中和 100pg/ml。自身 Abs 可中和未糖基化和糖基化的 IFN。我们还在 2267 名未感染儿童中的 4 名（0.2%）检测到中和 100pg/ml IFN-α2 的自身 Abs 和 45 名儿童（2%）中和 IFN-ω 的自身 Abs。因此，仅中和 IFN-α2 的自身 Abs 与危及生命的 COVID-19 肺炎的比值比（OR）更高（OR[95%CI] = 67.6[5.7-9,196.6]），而仅中和 IFN-ω 的自身 Abs 的比值比（OR[95%CI] = 2.6[1.2-5.3]）。中和高浓度 IFN-ω 和/或 IFN-α2 的自身 Abs 的比值比（OR[95%CI] = 12.9[4.6-35.9]）也高于中和低浓度 IFN-ω 和/或 IFN-α2 的自身 Abs 的比值比（OR[95%CI] = 5.5[3.1-9.6]）。