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Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency

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dc.contributor.authorLe Voyer, Tom
dc.contributor.authorParent, Audrey V.
dc.contributor.authorLiu, Xian
dc.contributor.authorCederholm, Axel
dc.contributor.authorGervais, Adrian
dc.contributor.authorRosain, Jérémie
dc.contributor.authorNguyen, Tina
dc.contributor.authorPerez Lorenzo, Malena
dc.contributor.authorElze Rackaityte, Elze
dc.contributor.authorRinchai, Darawan
dc.contributor.authorZhang, Peng
dc.contributor.authorBizien, Lucy
dc.contributor.authorHancioglu, Gonca
dc.contributor.authorGhillani-Dalbin, Pascale
dc.contributor.authorCharuel, Jean-Luc
dc.contributor.authorPhilippot, Quentin
dc.contributor.authorSokhna Gueye, Mame
dc.contributor.authorRaj Luxman, Majistor
dc.contributor.authorMaglorius Renkilaraj
dc.contributor.authorOgishi, Masato
dc.contributor.authorSoudée, Camille
dc.contributor.authorMigaud, Mélanie
dc.contributor.authorRozenberg, Flore
dc.contributor.authorMomenilandi, Mana
dc.contributor.authorRiller, Quentin
dc.contributor.authorImberti, Luisa
dc.contributor.authorDelmonte, Otavia M.
dc.contributor.authorMüller, Gabriele
dc.contributor.authorKeller, Baerbel
dc.contributor.authorOrrego, Julio
dc.contributor.authorFranco Gallego, William Alexander
dc.contributor.authorRubin, Tamar
dc.contributor.authorEmiroglu, Melike
dc.contributor.authorParvaneh, Nima
dc.contributor.authorEriksson, Daniel
dc.contributor.authorAranda-Guillen, Maribel
dc.contributor.authorBerrios, David I.
dc.contributor.authorVong, Linda
dc.contributor.authorKatelaris, Constance H.
dc.contributor.authorMustillo, Peter
dc.contributor.authorJohannes Raedler, Jonathan
dc.contributor.authorBohlen, Jonathan
dc.contributor.authorCelik, Jale Bengi
dc.contributor.authorAstudillo, Camila
dc.date.accessioned2024-06-03T17:26:55Z
dc.date.available2024-06-03T17:26:55Z
dc.date.issued2023
dc.descriptionSarah Winter, NF-κB Consortium, COVID Human Genetic Effort, 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
dc.description.abstractPatients with autoimmune polyendocrinopathy syndrome type 1 (APS-1) caused by autosomal recessive AIRE deficiency produce autoantibodies that neutralize type I interferons (IFNs)1,2, conferring a predisposition to life-threatening COVID-19 pneumonia3. 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, p52LOF/IκBδGOF). By contrast, neutralizing autoantibodies against type I IFNs are not found in individuals who are heterozygous for NFKB2 variants causing haploinsufficiency of p100 and p52 (hereafter, p52LOF/IκBδLOF) or gain-of-function of p52 (hereafter, p52GOF/IκBδLOF). 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.
dc.description.versionVersión publicada
dc.format.extent32 p.
dc.identifier.citationLe Voyer, T., Parent, A.V., Liu, X. et al. Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency. Nature 623, 803–813 (2023). https://doi.org/10.1038/s41586-023-06717-x
dc.identifier.doihttps://doi.org/10.1038/s41586-023-06717-x
dc.identifier.urihttps://hdl.handle.net/11447/8996
dc.language.isoen
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subjectAutoimmune polyendocrinopathy syndrome type 1
dc.subjectAPS-1
dc.titleAutoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency
dc.typeArticle
dcterms.accessRightsAcceso abierto
dcterms.sourceNature
dspace.entity.typePublication

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