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. 2023 Nov 8;623(7988):803–813. doi: 10.1038/s41586-023-06717-x

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 4 — a, The number of patients with a p52^LOF/IκBδ^GOF variant and manifestations of viral diseases as a function of their AAN-I-IFN status. b, Clinical and immunological manifestations in patients with a p52^LOF/IκBδ^GOF variant, as a function of their AAN-I-IFN status. Autoimm., autoimmunity; ecto. dyspl., ectodermal dysplasia; hypogam., hypogammaglobulinaemia; hypox., hypoxaemic; rec., recurrent; RTI, recurrent bacterial respiratory tract infection. c, Chord diagram of the main clinical and immunological manifestations of patients with inborn errors of NF-κB2. d, Anti-IFNα-2 IgG detection by Gyros in positive control individuals (n = 10), healthy control individuals (n = 7), patients with a p52^LOF/IκBδ^GOF (n = 9), p52^LOF/IκBδ^LOF (n = 2), p52^GOF/IκBδ^LOF (n = 2) or neutral (n = 2) NF-κB2 variant and COVID-19, as a function of disease severity. e, Heat map showing the type I IFN neutralization profile of unvaccinated patients during COVID-19, according to disease severity and clinical presentation during infection, including patients with a p52^LOF/IκBδ^GOF (n = 9), p52^GOF/IκBδ^LOF (n = 2) or p52^LOF/IκBδ^LOF (n = 2) variant. The red squares indicate a complete neutralization ability of the plasma for ISRE induction in the luciferase reporter assay system, and the white squares indicate a total absence of neutralizing autoantibody detection in the ISRE–luciferase assay. f, The viral load and IFN score in nasal swabs over the course of SARS-CoV-2 infection in patients with a p52^LOF/IκBδ^GOF variant (n = 2) with AAN-I-IFNs, and in vaccinated individuals with a mild disease and no AAN-I-IFNs (n = 4). g, The IFN score and viral load in whole blood (left) or nasal swabs (right) over the course of SARS-CoV2 infection in patients with a p52^LOF/IκBδ^GOF variant with AAN-I-IFNs (n = 2), or in individuals infected with SARS-CoV-2 presenting only mild disease (n = 36). The vertical arrows indicate the times of recombinant human IFNβ (rhIFNβ) injection and the arrowheads indicate the infusion of monoclonal antibodies (mAbs) against SARS-CoV-2 spike protein.