| Title: |
Autoantibodies against type I IFNs in humans with alternative NF-κB pathway deficiency |
| Authors: |
Le Voyer, Tom; Parent, Audrey, V; Liu, Xian; Cederholm, Axel; Gervais, Adrian; Rosain, Jérémie; Nguyen, Tina; Perez Lorenzo, Malena; Rackaityte, Elze; Rinchai, Darawan; Zhang, Peng; Bizien, Lucy; Hancioglu, Gonca; Ghillani-Dalbin, Pascale; Charuel, Jean-Luc; Philippot, Quentin; Gueye, Mame Sokhna; Maglorius Renkilaraj, Majistor Raj Luxman; Ogishi, Masato; Soudée, Camille; Migaud, Mélanie; Rozenberg, Flore; Momenilandi, Mana; Riller, Quentin; Imberti, Luisa; Delmonte, Ottavia, M; Müller, Gabriele; Keller, Baerbel; Orrego, Julio; Franco Gallego, William Alexander; Rubin, Tamar; Emiroglu, Melike; Parvaneh, Nima; Eriksson, Daniel; Aranda-Guillen, Maribel; Berrios, David, I; Vong, Linda; Katelaris, Constance, H; Mustillo, Peter; Raedler, Johannes; Bohlen, Jonathan; 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, Corey; Feng, Yi; Guichard, Audrey; Béziat, Vivien; Bustamante, Jacinta; Pan-Hammarström, Qiang; Zhang, Yu; Rosen, Lindsey, B; Holland, Steve, M; Bosticardo, Marita; Kenney, Heather; Castagnoli, Riccardo; Slade, Charlotte, A; Boztuğ, Kaan; Mahlaoui, Nizar; Latour, Sylvain; Abraham, Roshini, S; Lougaris, Vassilios; Hauck, Fabian; Atschekzei, Faranaz; Sogkas, Georgios; Poli, M. Cecilia; Slatter, Mary, A; Palterer, Boaz; Keller, Michael, D; Pinzon-Charry, Alberto; Sullivan, Anna; Droney, Luke; Suan, Daniel; Wong, Melanie; Kane, Alisa; Hu, Hannah; Ma, Cindy; Grombiříková, Hana; Ciznar, Peter; Dalal, Ilan; Aladjidi, Nathalie; Hie, Miguel; Lazaro, Estibaliz; Franco, José, Luis; Keles, Sevgi; Malphettes, Marion; Pasquet, Marlene; Maccari, Maria Elena; Meinhardt, Andrea; Ikinciogullari, Aydan; Shahrooei, Mohammad; Celmeli, Fatih; Frosk, Patrick; Goodnow, Christopher, C; Gray, Paul, E; Belot, Alexandre; 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, Charlotte; Rieux-Laucat, Frédéric; Tangye, Stuart, G; Sobacchi, Cristina; Doffinger, Rainer; Warnatz, Klaus; Grimbacher, Bodo; Fieschi, Claire; Berteloot, Laureline; Bryant, Vanessa, L; Trouillet Assant, Sophie; Neven, Benedicte; Abel, Laurent; Zhang, Qian; Boisson, Bertrand; Cobat, Aurélie; Jouanguy, Emmanuelle; Kampe, Olle; Roifman, Chaim, M; Landegren, Nils; Notarangelo, Luigi, D; Anderson, Mark, S; Casanova, Jean-Laurent; Puel, Anne |
| Contributors: |
Human genetics of infectious diseases : Mendelian predisposition (Equipe Inserm U1163); Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163); Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité); Centre International de Recherche en Infectiologie (CIRI); École normale supérieure de Lyon (ENS de Lyon); Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS); Virology and human respiratory Pathologies - Virology and human respiratory Pathologies CIRI (CIRI-VirPath); Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon); Activation et transduction du signal dans les lymphocytes - Lymphocyte activation and signaling CIRI (CIRI-LYACTS); Hospices Civils de Lyon (HCL); ANR-20-CO11-0001,AABIFNCOV,Bases génétiques et immunologiques des auto-anticorps contre les interférons de type I prédisposant aux formes sévères de COVID-19.(2020); ANR-21-LIBA-0002,AAILC,Autoanticorps contre les interférons de type I chez les patients libanais hospitalisés pour COVID-19.(2021); ANR-22-CE15-0046,AI2D,Autoanticorps anti-interférons et maladies infectieuses associées(2022); ANR-20-CE93-0003,GENVIR,Analyse multi-omique de l'immunité anti-virale: de l'identification des circuits biologiques pertinents à la découverte de défauts monogéniques héréditaires de l'immunité chez les patients avec infections virales sévères(2020); ANR-14-CE14-0026,Lumugene,Etude de familles multiplex de lupus pour l'identification de nouveaux gènes à fort impact phénotypique : de la découvertes des gènes à leurs fonctions(2014); ANR-18-CE17-0001,ACTION,Cytopénies Auto-immunes: génétique et mécanismes physiopathologiques du syndrome d'Evans pédaitrique(2018); ANR-18-RHUS-0010,ATRACTION,Autoimmunity/inflammation Through Rnaseq Analysis at the single Cell level for Therapeutic Innovation(2018); ANR-22-CE15-0047,BREAK-ITP,Décrypter la rupture de tolérance dans la thrombopénie immunologique(BREAK-TOL)(2022) |
| Source: |
ISSN: 0028-0836. |
| Publisher Information: |
CCSD; Nature Publishing Group |
| Publication Year: |
2023 |
| Collection: |
Université Jean Monnet – Saint-Etienne: HAL |
| Subject Terms: |
[SDV]Life Sciences [q-bio] |
| Description: |
International audience ; Abstract Patients 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 pneumonia 3 . 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 LOF /IκBδ GOF ). 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, p52 LOF /IκBδ LOF ) or gain-of-function of p52 (hereafter, p52 GOF /IκBδ LOF ). 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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41586-023-06717-x |
| Availability: |
https://hal.science/hal-04815868; https://hal.science/hal-04815868v1/document; https://hal.science/hal-04815868v1/file/41586_2023_Article_6717.pdf; https://doi.org/10.1038/s41586-023-06717-x |
| Rights: |
https://about.hal.science/hal-authorisation-v1/ ; info:eu-repo/semantics/OpenAccess |
| Accession Number: |
edsbas.5B326160 |
| Database: |
BASE |