Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency
Journal
Nature
ISSN
0028-0836
1476-4687
Date Issued
2023
Author(s)
Tom Le Voyer
Audrey V. Parent
Xian Liu
Axel Cederholm
Adrian Gervais
Jérémie Rosain
Tina Nguyen
Malena Perez Lorenzo
Elze Rackaityte
Darawan Rinchai
Peng Zhang
Lucy Bizien
Gonca Hancioglu
Pascale Ghillani-Dalbin
Jean-Luc Charuel
Quentin Philippot
Mame Sokhna Gueye
Majistor Raj Luxman Maglorius Renkilaraj
Masato Ogishi
Camille Soudée
Mélanie Migaud
Flore Rozenberg
Mana Momenilandi
Quentin Riller
Luisa Imberti
Ottavia M. Delmonte
Gabriele Müller
Baerbel Keller
Julio Orrego
William Alexander Franco Gallego
Tamar Rubin
Melike Emiroglu
Nima Parvaneh
Daniel Eriksson
Maribel Aranda-Guillen
David I. Berrios
Linda Vong
Constance H. Katelaris
Peter Mustillo
Johannes Raedler
Jonathan Bohlen
Jale Bengi Celik
Camila Astudillo
Sarah Winter
Stéphanie Boisson-Dupuis
Eric Oksenhendler
Satoshi Okada
Oana Caluseriu
Mathilde Valeria Ursini
Eric Ballot
Geoffroy Lafarge
Tomas Freiberger
Carlos A. Arango-Franco
Romain Levy
Alessandro Aiuti
Saleh Al-Muhsen
Fahd Al-Mulla
Evangelos Andreakos
Andrés A. Arias
Hagit Baris Feldman
Paul Bastard
Anastasia Bondarenko
Alessandro Borghesi
Ahmed A. Bousfiha
Petter Brodin
Yenan Bryceson
Giorgio Casari
John Christodoulou
Roger Colobran
Antonio Condino-Neto
Jacques Fellay
Carlos Flores
José Luis Franco
Filomeen Haerynck
Rabih Halwani
Lennart Hammarström
James R. Heath
Elena W. Y. Hsieh
Yuval Itan
Elżbieta Kaja
Kai Kisand
Cheng-Lung Ku
Yun Ling
Yu-Lung Lau
Davood Mansouri
Isabelle Meyts
Joshua D. Milner
Trine H. Mogensen
Antonio Novelli
Giuseppe Novelli
Keisuke Okamoto
Tayfun Ozcelik
Rebeca Perez de Diego
Jordi Perez-Tur
David S. Perlin
Carolina Prando
Aurora Pujol
Lluis Quintana-Murci
Laurent Renia
Igor Resnick
Carlos Rodríguez-Gallego
Vanessa Sancho-Shimizu
Anna Sediva
Mikko R. J. Seppänen
Mohammed Shahrooei
Anna Shcherbina
Pere Soler Palacín
Graziano Pesole
András N. Spaan
Helen C. Su
Ivan Tancevski
Ahmad Abou Tayoun
Ali Amara
Guy Gorochov
Şehime Gülsün Temel
Christian Thorball
Pierre Tiberghien
Sophie Trouillet-Assant
Stuart Turvey
K. M. Furkan Uddin
Mohammed J. Uddin
Diederik van de Beek
Mateus Vidigal
Donald C. Vinh
Horst von Bernuth
Joost Wauters
Mayana Zatz
Shen-Ying Zhang
Lisa F. P. Ng
Catriona McLean
Aurélien Guffroy
Joseph L. DeRisi
David Yu
Corey Miller
Yi Feng
Audrey Guichard
Vivien Béziat
Jacinta Bustamante
Qiang Pan-Hammarström
Yu Zhang
Lindsey B. Rosen
Steve M. Holland
Marita Bosticardo
Heather Kenney
Riccardo Castagnoli
Charlotte A. Slade
Kaan Boztuğ
Nizar Mahlaoui
Sylvain Latour
Roshini S. Abraham
Vassilios Lougaris
Fabian Hauck
Anna Sediva
Faranaz Atschekzei
Georgios Sogkas
M. Cecilia Poli
Mary A. Slatter
Boaz Palterer
Michael D. Keller
Alberto Pinzon-Charry
Anna Sullivan
Luke Droney
Daniel Suan
Melanie Wong
Alisa Kane
Hannah Hu
Cindy Ma
Hana Grombiříková
Peter Ciznar
Ilan Dalal
Nathalie Aladjidi
Miguel Hie
Estibaliz Lazaro
Jose Franco
Sevgi Keles
Marion Malphettes
Marlene Pasquet
Maria Elena Maccari
Andrea Meinhardt
Aydan Ikinciogullari
Mohammad Shahrooei
Fatih Celmeli
Patrick Frosk
Christopher C. Goodnow
Paul E. Gray
Alexandre Belot
Hye Sun Kuehn
Sergio D. Rosenzweig
Makoto Miyara
Francesco Licciardi
Amélie Servettaz
Vincent Barlogis
Guillaume Le Guenno
Vera-Maria Herrmann
Taco Kuijpers
Grégoire Ducoux
Françoise Sarrot-Reynauld
Catharina Schuetz
Charlotte Cunningham-Rundles
Frédéric Rieux-Laucat
Stuart G. Tangye
Cristina Sobacchi
Rainer Doffinger
Klaus Warnatz
Bodo Grimbacher
Claire Fieschi
Laureline Berteloot
Vanessa L. Bryant
Sophie Trouillet Assant
Helen Su
Benedicte Neven
Laurent Abel
Qian Zhang
Bertrand Boisson
Aurélie Cobat
Emmanuelle Jouanguy
Olle Kampe
Paul Bastard
Chaim M. Roifman
Nils Landegren
Luigi D. Notarangelo
Mark S. Anderson
Jean-Laurent Casanova
Anne Puel
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:title>Abstract</jats:title><jats:p>Patients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)<jats:sup>1,2</jats:sup>, conferring a predisposition to life-threatening COVID-19 pneumonia<jats:sup>3</jats:sup>. Here we report that patients with autosomal recessive NIK or RELB deficiency, or a specific type of autosomal-dominant NF-κB2 deficiency, also have neutralizing autoantibodies against type I IFNs and are at higher risk of getting life-threatening COVID-19 pneumonia. In patients with autosomal-dominant NF-κB2 deficiency, these autoantibodies are found only in individuals who are heterozygous for variants associated with both transcription (p52 activity) loss of function (LOF) due to impaired p100 processing to generate p52, and regulatory (IκBδ activity) gain of function (GOF) due to the accumulation of unprocessed p100, therefore increasing the inhibitory activity of IκBδ (hereafter, p52<jats:sup>LOF</jats:sup>/IκBδ<jats:sup>GOF</jats:sup>). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for <jats:italic>NFKB2</jats:italic> variants causing haploinsufficiency of p100 and p52 (hereafter, p52<jats:sup>LOF</jats:sup>/IκBδ<jats:sup>LOF</jats:sup>) or gain-of-function of p52 (hereafter, p52<jats:sup>GOF</jats:sup>/IκBδ<jats:sup>LOF</jats:sup>). In contrast to patients with APS-1, patients with disorders of NIK, RELB or NF-κB2 have very few tissue-specific autoantibodies. However, their thymuses have an abnormal structure, with few AIRE-expressing medullary thymic epithelial cells. Human inborn errors of the alternative NF-κB pathway impair the development of AIRE-expressing medullary thymic epithelial cells, thereby underlying the production of autoantibodies against type I IFNs and predisposition to viral diseases.</jats:p>
Subjects
autoantibodies
;
covid-19
;
humans
;
interferon type i
;
nf-kappa b
;
nf-kappa b p52 subunit
;
pneumonia
;
autoantibody
;
immunoglobulin enhancer binding protein
;
interferon
;
coronavirus disease 2019
;
genetics
;
human
;
metabolism
;
pneumonia