Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency
Author:
Le Voyer TomORCID, Parent Audrey V.ORCID, Liu Xian, Cederholm AxelORCID, Gervais Adrian, Rosain Jérémie, Nguyen Tina, Perez Lorenzo MalenaORCID, Rackaityte ElzeORCID, Rinchai Darawan, Zhang PengORCID, Bizien Lucy, Hancioglu GoncaORCID, Ghillani-Dalbin Pascale, Charuel Jean-Luc, Philippot Quentin, Gueye Mame SokhnaORCID, Maglorius Renkilaraj Majistor Raj Luxman, Ogishi Masato, Soudée Camille, Migaud MélanieORCID, Rozenberg Flore, Momenilandi Mana, Riller QuentinORCID, Imberti Luisa, Delmonte Ottavia M., Müller Gabriele, Keller Baerbel, Orrego Julio, Franco Gallego William Alexander, Rubin Tamar, Emiroglu MelikeORCID, Parvaneh NimaORCID, Eriksson Daniel, Aranda-Guillen MaribelORCID, Berrios David I., Vong Linda, Katelaris Constance H.ORCID, Mustillo Peter, Raedler JohannesORCID, Bohlen JonathanORCID, Bengi Celik Jale, Astudillo Camila, Winter Sarah, Boisson-Dupuis Stéphanie, Oksenhendler Eric, Okada Satoshi, Caluseriu Oana, Ursini Mathilde Valeria, Ballot Eric, Lafarge Geoffroy, Freiberger Tomas, Arango-Franco Carlos A., Levy Romain, Aiuti Alessandro, Al-Muhsen Saleh, Al-Mulla Fahd, Andreakos Evangelos, Arias Andrés A., Feldman Hagit Baris, Bastard Paul, Bondarenko Anastasia, Borghesi Alessandro, Bousfiha Ahmed A., Brodin Petter, Bryceson Yenan, Casari Giorgio, Christodoulou John, Colobran Roger, Condino-Neto Antonio, Fellay Jacques, Flores Carlos, Franco José Luis, Haerynck Filomeen, Halwani Rabih, Hammarström Lennart, Heath James R., Hsieh Elena W. Y., Itan Yuval, Kaja Elżbieta, Kisand Kai, Ku Cheng-Lung, Ling Yun, Lau Yu-Lung, Mansouri Davood, Meyts Isabelle, Milner Joshua D., Mogensen Trine H., Novelli Antonio, Novelli Giuseppe, Okamoto Keisuke, Ozcelik Tayfun, de Diego Rebeca Perez, Perez-Tur Jordi, Perlin David S., Prando Carolina, Pujol Aurora, Quintana-Murci Lluis, Renia Laurent, Resnick Igor, Rodríguez-Gallego Carlos, Sancho-Shimizu Vanessa, Sediva Anna, Seppänen Mikko R. J., Shahrooei Mohammed, Shcherbina Anna, Palacín Pere Soler, Pesole Graziano, Spaan András N., Su Helen C., Tancevski Ivan, Tayoun Ahmad Abou, Amara Ali, Gorochov Guy, Temel Şehime Gülsün, Thorball Christian, Tiberghien Pierre, Trouillet-Assant Sophie, Turvey Stuart, Uddin K. M. Furkan, Uddin Mohammed J., van de Beek Diederik, Vidigal Mateus, Vinh Donald C., von Bernuth Horst, Wauters Joost, Zatz Mayana, Zhang Shen-Ying, Ng Lisa F. P., McLean Catriona, Guffroy Aurélien, DeRisi Joseph L., Yu David, Miller CoreyORCID, Feng Yi, Guichard Audrey, Béziat VivienORCID, Bustamante Jacinta, Pan-Hammarström QiangORCID, Zhang Yu, Rosen Lindsey B., Holland Steve M.ORCID, Bosticardo Marita, Kenney Heather, Castagnoli RiccardoORCID, Slade Charlotte A., Boztuğ Kaan, Mahlaoui Nizar, Latour Sylvain, Abraham Roshini S., Lougaris Vassilios, Hauck FabianORCID, Sediva AnnaORCID, Atschekzei Faranaz, Sogkas Georgios, Poli M. CeciliaORCID, Slatter Mary A., Palterer Boaz, Keller Michael D., Pinzon-Charry Alberto, Sullivan Anna, Droney LukeORCID, Suan Daniel, Wong Melanie, Kane Alisa, Hu Hannah, Ma CindyORCID, Grombiříková HanaORCID, Ciznar PeterORCID, Dalal Ilan, Aladjidi Nathalie, Hie Miguel, Lazaro EstibalizORCID, Franco JoseORCID, Keles SevgiORCID, Malphettes Marion, Pasquet Marlene, Maccari Maria Elena, Meinhardt AndreaORCID, Ikinciogullari Aydan, Shahrooei Mohammad, Celmeli FatihORCID, Frosk Patrick, Goodnow Christopher C.ORCID, Gray Paul E.ORCID, Belot AlexandreORCID, Kuehn Hye Sun, Rosenzweig Sergio D., Miyara Makoto, Licciardi Francesco, Servettaz Amélie, Barlogis Vincent, Le Guenno Guillaume, Herrmann Vera-Maria, Kuijpers Taco, Ducoux Grégoire, Sarrot-Reynauld Françoise, Schuetz Catharina, Cunningham-Rundles CharlotteORCID, Rieux-Laucat FrédéricORCID, Tangye Stuart G.ORCID, Sobacchi Cristina, Doffinger Rainer, Warnatz Klaus, Grimbacher Bodo, Fieschi Claire, Berteloot LaurelineORCID, Bryant Vanessa L., Trouillet Assant Sophie, Su HelenORCID, Neven Benedicte, Abel Laurent, Zhang Qian, Boisson BertrandORCID, Cobat AurélieORCID, Jouanguy Emmanuelle, Kampe OlleORCID, Bastard Paul, Roifman Chaim M., Landegren Nils, Notarangelo Luigi D.ORCID, Anderson Mark S.ORCID, Casanova Jean-LaurentORCID, Puel AnneORCID, , ,
Abstract
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.
Publisher
Springer Science and Business Media LLC
Subject
Multidisciplinary
Reference71 articles.
1. Levin, M. Anti-interferon auto-antibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. 3, e292 (2006). 2. Meager, A. et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. 3, e289 (2006). 3. Bastard, P. et al. Preexisting autoantibodies to type I IFNs underlie critical COVID-19 pneumonia in patients with APS-1. J. Exp. Med. 218, e20210554 (2021). 4. Puel, A., Bastard, P., Bustamante, J. & Casanova, J.-L. Human autoantibodies underlying infectious diseases. J. Exp. Med. 219, e20211387 (2022). 5. Mogensen, K. E., Daubas, P., Gresser, I., Sereni, D. & Varet, B. Patient with circulating antibodies to alpha-interferon. Lancet 318, 1227–1228 (1981).
Cited by
5 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|